L. F. Abrahao-machado and C. Scapulatempo-neto, HER2 testing in gastric cancer: An update, World J. Gastroenterol, vol.22, issue.19, pp.4619-4644, 2016.

K. Aertgeerts, R. Skene, J. Yano, B. C. Sang, H. Zou et al., Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein, J. Biol. Chem, vol.286, issue.21, pp.18756-18765, 2011.

D. B. Agus, R. W. Akita, W. D. Fox, G. D. Lewis, B. Higgins et al., Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth, Cancer Cell, vol.2, issue.2, pp.127-164, 2002.

Z. Ahmed, Z. Timsah, K. M. Suen, N. P. Cook, G. R. Lee et al., Grb2 monomer-dimer equilibrium determines normal versus oncogenic function, Nat. Commun, vol.6, p.7354, 2015.

T. Akiyama, S. Matsuda, Y. Namba, T. Saito, K. Toyoshima et al., The transforming potential of the c-erbB-2 protein is regulated by its autophosphorylation at the carboxyl-terminal domain, Mol. Cell. Biol, vol.11, issue.2, pp.833-875, 1991.

T. R. Alderson, J. H. Lee, C. Charlier, J. Ying, and A. Bax, Propensity for cis -Proline Formation in Unfolded Proteins, ChemBioChem, vol.19, issue.1, pp.37-42, 2018.

C. V. Alvarez, K. Shon, M. Miloso, and L. Beguinot, Structural Requirements of the Epidermal Growth Factor Receptor for Tyrosine Phosphorylation of eps8 and eps15 , Substrates Lacking Src SH2 Homology Domains, J. Biol. Chem, vol.270, issue.27, pp.16271-16276, 1995.

C. B. Anfinsen, Folding of Protein Chains. Science (80-. ), vol.181, pp.223-230, 1973.

A. Araújo, G. Oliva, F. Henrique-silva, R. Garratt, O. Cáceres et al., Influence of the Histidine Tail on the Structure and Activity of Recombinant Chlorocatechol 1,2-Dioxygenase, Biochem. Biophys. Res. Commun, vol.272, issue.2, pp.480-484, 2000.

A. Arkhipov, Y. Shan, R. Das, N. F. Endres, M. P. Eastwood et al., Architecture and membrane interactions of the EGF receptor, Cell, vol.152, issue.3, pp.557-569, 2013.

D. J. Arndt-jovin, M. G. Botelho, and T. M. Jovin, Structure-Function Relationships of ErbB RTKs in the Plasma Membrane of Living Cells, Cold Spring Harb. Perspect. Biol, vol.6, issue.4, pp.8961-008961, 2014.

A. Bah, R. M. Vernon, Z. Siddiqui, M. Krzeminski, R. Muhandiram et al., Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch, Nature, vol.519, pp.106-115, 2015.

C. I. Bargmann, M. Hung, and R. A. Weinberg, Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185, Cell, vol.45, issue.5, pp.649-657, 1986.

C. I. Bargmann and R. A. Weinberg, Increased tyrosine kinase activity associated with the protein encoded by the activated neu oncogene, Proc. Natl. Acad. Sci, vol.85, issue.15, pp.5394-5398, 1988.

R. R. Bartelt, J. Light, A. Vacaflores, A. Butcher, M. Pandian et al., Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands, Biochim. Biophys. Acta -Mol. Cell Res, vol.1853, issue.10, pp.2560-2569, 2015.

K. Bayer, P. De-koninck, A. S. Leonard, J. W. Hell, and H. Schulman, Interaction with the NMDA receptor locks CaMKII in an active conformation, Nature, vol.411, issue.6839, pp.801-805, 2001.

C. A. Bell, J. A. Tynan, K. C. Hart, A. N. Meyer, S. C. Robertson et al., Rotational Coupling of the Transmembrane and Kinase Domains of the Neu Receptor Tyrosine Kinase, Mol. Biol. Cell, vol.11, issue.10, pp.3589-3599, 2000.

A. Y. Belorusova, J. Osz, M. V. Petoukhov, C. Peluso-iltis, B. Kieffer et al., Solution Behavior of the Intrinsically Disordered N-Terminal Domain of Retinoid X Receptor ? in the Context of the Full-Length Protein, Biochemistry, vol.55, issue.12, pp.1741-1748, 2016.

H. Ben-bassat and B. Y. Klein, Inhibitors of tyrosine kinases in the treatment of psoriasis, Curr. Pharm. Des, vol.6, issue.9, pp.933-975, 2000.

A. P. Benfield, B. B. Whiddon, J. H. Clements, and S. F. Martin, Structural and energetic aspects of Grb2-SH2 domain-swapping, Arch. Biochem. Biophys, vol.462, issue.1, pp.47-53, 2007.

R. B. Berlow, H. J. Dyson, and P. E. Wright, Expanding the Paradigm: Intrinsically Disordered Proteins and Allosteric Regulation, J. Mol. Biol, vol.430, issue.16, pp.2309-2320, 2018.

P. Bernadó, C. W. Bertoncini, C. Griesinger, M. Zweckstetter, and M. Blackledge, Defining longrange order and local disorder in native alpha-synuclein using residual dipolar couplings, J. Am. Chem. Soc, vol.127, issue.51, pp.17968-17969, 2005.

P. Bernadó and M. Blackledge, A self-consistent description of the conformational behavior of chemically denatured proteins from NMR and small angle scattering, Biophys. J, vol.97, issue.10, pp.2839-2845, 2009.

P. Bernadó, E. Mylonas, M. V. Petoukhov, M. Blackledge, and D. I. Svergun, Structural characterization of flexible proteins using small-angle X-ray scattering, J. Am. Chem. Soc, vol.129, issue.17, pp.5656-5664, 2007.

P. J. Bertics, W. Weber, C. Cochet, and G. N. Gill, Regulation of the epidermal growth factor receptor by phosphorylation, J. Cell. Biochem, vol.29, issue.3, pp.195-208, 1985.

C. W. Bertoncini, Y. Jung, C. O. Fernandez, W. Hoyer, C. Griesinger et al., From The Cover: Release of long-range tertiary interactions potentiates aggregation of natively unstructured -synuclein, Proc. Natl. Acad. Sci, vol.102, issue.5, pp.1430-1435, 2005.

S. Bhattacharya and X. Lin, Recent advances in computational protocols addressing intrinsically disordered proteins, Biomolecules, vol.9, issue.4, 2019.

S. Bhoir, A. Shaik, V. Thiruvenkatam, and S. Kirubakaran, High yield bacterial expression, purification and characterisation of bioactive Human Tousled-like Kinase 1B involved in cancer, Sci. Rep, vol.8, issue.1, p.4796, 2018.

A. Bishayee, L. Beguinot, and S. Bishayee, Phosphorylation of Tyrosine 992, 1068, and 1086 Is Required for Conformational Change of the Human Epidermal Growth Factor Receptor C-Terminal Tail, Mol. Biol. Cell, vol.10, issue.3, pp.525-536, 1999.

W. T. Booth, C. R. Schlachter, S. Pote, N. Ussin, N. J. Mank et al., Impact of an N-terminal Polyhistidine Tag on Protein Thermal Stability, ACS Omega, vol.3, issue.1, pp.760-768, 2018.

A. Borgia, M. B. Borgia, K. Bugge, V. M. Kissling, P. O. Heidarsson et al., Extreme disorder in an ultra-high-affinity protein complex, Nature, vol.555, issue.7694, pp.61-66, 2017.

O. Bornet, M. Nouailler, M. Feracci, C. Sebban-kreuzer, D. Byrne et al., Identification of a Src kinase SH3 binding site in the C-terminal domain of the human ErbB2 receptor tyrosine kinase, FEBS Lett, vol.588, issue.12, pp.2031-2036, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01458194

P. E. Bragin, K. S. Mineev, O. V. Bocharova, P. E. Volynsky, E. V. Bocharov et al., HER2 Transmembrane Domain Dimerization Coupled with Self-Association of Membrane-Embedded Cytoplasmic Juxtamembrane Regions, J. Mol. Biol, vol.428, issue.1, pp.52-61, 2016.

P. J. Brennan, T. Kumogai, A. Berezov, R. Murali, and M. I. Greene, HER2/neu: Mechanisms of dimerization/oligomerization, Oncogene, vol.19, issue.53, pp.6093-6101, 2000.

P. S. Brignola, K. Lackey, S. H. Kadwell, C. Hoffman, E. Horne et al., Comparison of the Biochemical and Kinetic Properties of the Type 1 Receptor Tyrosine Kinase Intracellular Domains, J. Biol. Chem, vol.277, issue.2, pp.1576-1585, 2002.

P. S. Brignola, K. Lackey, S. H. Kadwell, C. Hoffman, E. Horne et al., Comparison of the Biochemical and Kinetic Properties of the Type 1 Receptor Tyrosine Kinase Intracellular Domains, J. Biol. Chem, vol.277, issue.2, pp.1576-1585, 2002.

S. Britsch, L. Li, S. Kirchhoff, F. Theuring, V. Brinkmann et al., The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system, Genes Dev, vol.12, issue.12, pp.1825-1861, 1998.

M. Brucale, B. Schuler, and B. Samorì, Single-Molecule Studies of Intrinsically Disordered Proteins, Chem. Rev, vol.114, issue.6, pp.3281-3317, 2014.

L. Buday and J. Downward, Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor, Cell, vol.73, issue.3, pp.611-631, 1993.

S. Burden and Y. Yarden, Neuregulins and their receptors: A versatile signaling module in organogenesis and oncogenesis, Neuron, vol.18, pp.847-855, 1997.

A. W. Burgess, H. Cho, C. Eigenbrot, K. M. Ferguson, T. P. Garrett et al., An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors, Mol. Cell, vol.12, issue.3, pp.541-52, 2003.

G. Burnett and E. P. Kennedy, The enzymatic phosphorylation of proteins, J. Biol. Chem, vol.211, issue.2, pp.969-80, 1954.

N. Buza, D. M. Roque, and A. D. Santin, HER2/ neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges, Arch. Pathol. Lab. Med, vol.138, issue.3, pp.343-350, 2014.

C. Camilloni, A. De-simone, W. F. Vranken, and M. Vendruscolo, Determination of Secondary Structure Populations in Disordered States of Proteins Using Nuclear Magnetic Resonance Chemical Shifts, Biochemistry, vol.51, issue.11, pp.2224-2231, 2012.

P. Carter, L. Presta, C. M. Gorman, J. B. Ridgway, D. Henner et al., Humanization of an anti-p185HER2 antibody for human cancer therapy, Proc. Natl. Acad. Sci. U. S. A, vol.89, issue.10, pp.4285-4289, 1992.

P. Caspers, M. Stieger, and P. Burn, Overproduction of bacterial chaperones improves the solubility of recombinant protein tyrosine kinases in Escherichia coli, Cell. Mol. Biol, vol.40, issue.5, pp.635-679, 1994.

R. Chan, W. R. Hardy, M. A. Laing, S. E. Hardy, and W. J. Muller, The Catalytic Activity of the ErbB-2 Receptor Tyrosine Kinase Is Essential for Embryonic Development, Mol. Cell. Biol, vol.22, issue.4, pp.1073-1078, 2002.

J. P. Changeux, The feedback control mechanisms of biosynthetic L-threonine deaminase by Lisoleucine, Cold Spring Harb. Symp. Quant. Biol, vol.26, pp.313-321, 1961.

P. Chardin, J. Camonis, N. Gale, L. Van-aelst, J. Schlessinger et al., Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2, Science, vol.260, issue.5112, pp.1338-1343, 1993.

A. Charest, J. Wagner, S. Jacob, C. J. Mcglade, and M. L. Tremblay, Phosphotyrosineindependent Binding of SHC to the NPLH Sequence of Murine Protein-tyrosine Phosphatase-PEST, J. Biol. Chem, vol.271, issue.14, pp.8424-8429, 1996.

A. R. Chaudhury, K. M. Gerecke, J. M. Wyss, D. G. Morgan, M. N. Gordon et al., Neuregulin-1 and ErbB4 Immunoreactivity Is Associated with Neuritic Plaques in Alzheimer Disease Brain and in a Transgenic Model of Alzheimer Disease, J. Neuropathol. Exp. Neurol, vol.62, issue.1, pp.42-54, 2003.

A. Chausovsky, H. Waterman, M. Elbaum, Y. Yarden, B. Geiger et al., Molecular requirements for the effect of neuregulin on cell spreading, motility and colony organization, Oncogene, vol.19, issue.7, pp.878-888, 2000.

C. Chen, Z. Zhou, R. Liu, Y. Li, P. B. Azmi et al., The WW domain containing E3 ubiquitin protein ligase 1 upregulates ErbB2 and EGFR through RING finger protein 11, Oncogene, vol.27, issue.54, pp.6845-6855, 2008.

Z. Chen and P. A. Cole, Synthetic approaches to protein phosphorylation, Curr. Opin. Chem. Biol, vol.28, issue.3, pp.115-137, 2015.

A. M. Cheng, T. M. Saxton, R. Sakai, S. Kulkarni, G. Mbamalu et al., Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation, Cell, vol.95, issue.6, pp.793-803, 1998.

K. Cheng and J. G. Koland, Nucleotide Binding by the Epidermal Growth Factor Receptor Proteintyrosine Kinase, J. Biol. Chem, vol.271, issue.1, pp.311-318, 1996.

H. Cho, K. Mason, K. X. Ramyar, A. M. Stanley, S. B. Gabelli et al., Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab, Nature, vol.421, issue.6924, pp.756-760, 2003.

J. J. Chou, S. Gaemers, B. Howder, J. M. Louis, and A. Bax, A simple apparatus for generating stretched polyacrylamide gels, yielding uniform alignment of proteins and detergent micelles, J. Biomol. NMR, vol.21, issue.4, pp.377-382, 2001.

S. Cohen, R. A. Fava, and S. T. Sawyer, Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver, Proc. Natl. Acad. Sci. U. S. A, vol.79, issue.20, pp.6237-6278, 1982.

C. M. Connell and G. J. Doherty, Activating HER2 mutations as emerging targets in multiple solid cancers, ESMO Open, vol.2, issue.5, p.279, 2017.

T. N. Cordeiro, F. Herranz-trillo, A. Urbanek, A. Estaña, J. Cortés et al., , 2017.

, Small-angle scattering studies of intrinsically disordered proteins and their complexes, Curr. Opin. Struct. Biol, vol.42, pp.15-23

F. Cordier, A. Chaffotte, E. Terrien, C. Préhaud, F. X. Theillet et al., Ordered phosphorylation events in two independent cascades of the PTEN C-tail revealed by NMR, J. Am. Chem. Soc, vol.134, issue.50, pp.20533-20543, 2012.

F. Cordier, A. Chaffotte, and N. Wolff, Quantitative and dynamic analysis of PTEN phosphorylation by NMR, pp.82-91, 2015.

D. Cussac, M. Frech, and P. Chardin, Binding of the Grb2 SH2 domain to phosphotyrosine motifs does not change the affinity of its SH3 domains for Sos proline-rich motifs, EMBO J, vol.13, issue.17, pp.4011-4021, 1994.

H. Dai, H. Ding, X. W. Meng, S. Lee, P. A. Schneider et al., Contribution of Bcl-2 Phosphorylation to Bak Binding and Drug Resistance, Cancer Res, vol.73, issue.23, pp.6998-7008, 2013.

R. J. Daly, M. D. Binder, and R. L. Sutherland, Overexpression of the Grb2 gene in human breast cancer cell lines, Oncogene, vol.9, issue.9, pp.2723-2730, 1994.

D. Dankort, N. Jeyabalan, N. Jones, D. J. Dumont, and W. J. Muller, Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins, J. Biol. Chem, vol.276, issue.42, pp.38921-38928, 2001.

D. Dankort, B. Maslikowski, N. Warner, N. Kanno, H. Kim et al., Grb2 and Shc Adapter Proteins Play Distinct Roles in Neu ( ErbB-2 ) -Induced Mammary Tumorigenesis : Implications for Human Breast Cancer, Mol. Cell. Biol, vol.21, issue.5, pp.1540-1551, 2001.

D. L. Dankort, Z. Wang, V. Blackmore, M. F. Moran, and W. J. Muller, Distinct tyrosine autophosphorylation sites negatively and positively modulate neu-mediated transformation, Mol. Cell. Biol, vol.17, issue.9, pp.5410-5425, 1997.

G. David and J. Pérez, Combined sampler robot and high-performance liquid chromatography: a fully automated system for biological small-angle X-ray scattering experiments at the Synchrotron SOLEIL SWING beamline, J. Appl. Crystallogr, vol.42, issue.5, pp.892-900, 2009.

P. E. Dawson, T. W. Muir, I. Clark-lewis, and S. B. Kent, Synthesis of proteins by native chemical ligation, Science, vol.266, issue.5186, pp.776-785, 1994.

A. De-biasio, A. I. De-opakua, G. B. Mortuza, R. Molina, T. N. Cordeiro et al., Structure of p15PAF-PCNA complex and implications for clamp sliding during DNA replication and repair, Nat. Commun, vol.6, p.6439, 2015.

E. Delaforge, J. Kragelj, L. Tengo, A. Palencia, S. Milles et al., Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy, J. Am. Chem. Soc, vol.140, issue.3, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01726157

J. Den-hertog and T. Hunter, Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the SH2 and C-terminal SH3 domains, EMBO J, vol.15, issue.12, pp.3016-3043, 1996.

L. Deshmukh, N. Meller, N. Alder, T. Byzova, and O. Vinogradova, Tyrosine Phosphorylation as a Conformational Switch, J. Biol. Chem, vol.286, issue.47, pp.40943-40953, 2011.

C. Deville, Etude des états multiples des domaines WH2 en interaction avec l'actine par résonnance magnétique nucléaire, 2015.

D. Fiore, P. Pierce, J. Kraus, M. Segatto, O. King et al., erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells, Science, vol.237, issue.4811, pp.178-182, 1987.

D. Didry, F. Cantrelle, C. Husson, P. Roblin, A. M. Moorthy et al., How a single residue in individual ? -thymosin/WH2 domains controls their functions in actin assembly, EMBO J, vol.31, issue.4, pp.1000-1013, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00692490

V. I. Dodero, Biomolecular studies by circular dichroism, Front. Biosci, vol.16, issue.1, p.61, 2011.

J. Dogan, S. Gianni, J. , and P. , The binding mechanisms of intrinsically disordered proteins, Phys. Chem. Chem. Phys, vol.16, issue.14, pp.6323-6331, 2014.

Z. Dosztányi, V. Csizmok, P. Tompa, and I. Simon, IUPred: Web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content, Bioinformatics, vol.21, issue.16, pp.3433-3434, 2005.

J. Downward, Y. Yarden, E. Mayes, G. Scrace, N. Totty et al., Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences, Nature, vol.307, issue.5951, pp.521-527, 1984.

Z. Du and C. M. Lovly, Mechanisms of receptor tyrosine kinase activation in cancer, Mol. Cancer, vol.17, issue.1, p.58, 2018.

J. Duneau, A. P. Vegh, and J. N. Sturgis, A Dimerization Hierarchy in the Transmembrane Domains of the HER Receptor Family, Biochemistry, vol.46, issue.7, pp.2010-2019, 2007.

A. Dunker, J. Lawson, C. J. Brown, R. M. Williams, P. Romero et al., Intrinsically disordered protein. J. Mol. Graph. Model, vol.19, issue.1, pp.26-59, 2001.

D. Durand, C. Vivès, D. Cannella, J. Pérez, E. Pebay-peyroula et al., NADPH oxidase activator p67phox behaves in solution as a multidomain protein with semi-flexible linkers, J. Struct. Biol, vol.169, issue.1, pp.45-53, 2010.

H. J. Dyson and P. E. Wright, Intrinsically unstructured proteins and their functions, Nat. Rev. Mol. Cell Biol, vol.6, issue.3, pp.197-208, 2005.

W. Eckhart, M. A. Hutchinson, and T. Hunter, An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates, Cell, vol.18, issue.4, pp.925-933, 1979.

M. D. Ehlers, S. Zhang, J. P. Bernhardt, and R. L. Huganir, Inactivation of NMDA Receptors by Direct Interaction of Calmodulin with the NR1 Subunit, Cell, vol.84, issue.5, pp.745-755, 1996.

N. F. Endres, R. Das, A. W. Smith, A. Arkhipov, E. Kovacs et al., Conformational Coupling across the Plasma Membrane in Activation of the EGF Receptor, Cell, vol.152, issue.3, pp.543-556, 2013.

S. Escrivá-de-romaní, M. Arumí, M. Bellet, and C. Saura, HER2-positive breast cancer: Current and new therapeutic strategies, The Breast, vol.39, pp.80-88, 2018.

Y. Fan, L. Wong, J. Ding, N. A. Spiridonov, R. C. Johnson et al., Mutational Activation of ErbB2 Reveals a New Protein Kinase Autoinhibition Mechanism, J. Biol. Chem, vol.283, issue.3, pp.1588-1596, 2008.

S. Felder, M. Zhou, P. Hu, J. Ureña, A. Ullrich et al., SH2 domains exhibit high-affinity binding to tyrosine-phosphorylated peptides yet also exhibit rapid dissociation and exchange, Mol. Cell. Biol, vol.13, issue.3, pp.1449-1455, 1993.

M. Feracci, C. Pimentel, O. Bornet, P. Roche, D. Salaun et al., MEMO associated with an ErbB2 receptor phosphopeptide reveals a new phosphotyrosine motif, FEBS Lett, vol.585, issue.17, pp.2688-92, 2011.
URL : https://hal.archives-ouvertes.fr/hal-01458275

K. M. Ferguson, Extracellular domains drive homo-but not hetero-dimerization of erbB receptors, EMBO J, vol.19, issue.17, pp.4632-4643, 2000.

K. M. Ferguson, M. B. Berger, J. M. Mendrola, H. Cho, D. J. Leahy et al., EGF Activates Its Receptor by Removing Interactions that Autoinhibit Ectodomain Dimerization, Mol. Cell, vol.11, issue.2, pp.507-517, 2003.

E. Fischer, Einfluss der Configuration auf die Wirkung der Enzyme, Berichte der Dtsch. Chem. Gesellschaft, vol.27, issue.3, pp.2985-2993, 1894.

A. V. Fonin, A. L. Darling, I. M. Kuznetsova, K. K. Turoverov, and V. N. Uversky, Intrinsically disordered proteins in crowded milieu: when chaos prevails within the cellular gumbo, Cell. Mol. Life Sci, vol.75, issue.21, pp.3907-3929, 2018.

D. Franke, M. V. Petoukhov, P. V. Konarev, A. Panjkovich, A. Tuukkanen et al., ATSAS 2.8 : a comprehensive data analysis suite for small-angle scattering from macromolecular solutions, J. Appl. Crystallogr, vol.50, issue.4, pp.1212-1225, 2017.

M. C. Franklin, K. D. Carey, F. F. Vajdos, D. J. Leahy, A. M. De-vos et al., Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex, Cancer Cell, vol.5, issue.4, pp.317-328, 2004.

D. M. Freed, N. J. Bessman, A. Kiyatkin, E. Salazar-cavazos, P. O. Byrne et al., EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics, vol.171, pp.683-695, 2017.

D. Fushman, R. Weisemann, H. Thüring, and H. Rüterjans, Backbone dynamics of ribonuclease T1 and its complex with 2'GMP studied by two-dimensional heteronuclear NMR spectroscopy, J. Biomol. NMR, vol.4, issue.1, pp.61-78, 1994.

M. Fuxreiter, I. Simon, P. Friedrich, and P. Tompa, Preformed structural elements feature in partner recognition by intrinsically unstructured proteins, J. Mol. Biol, vol.338, issue.5, pp.1015-1026, 2004.

C. Gaboriaud, V. Bissery, T. Benchetrit, and J. P. Mornon, Hydrophobic cluster analysis: An efficient new way to compare and analyse amino acid sequences, FEBS Lett, vol.224, issue.1, pp.149-155, 1987.

K. S. Gajiwala, EGFR: Tale of the C-terminal tail, Protein Sci, vol.22, issue.7, pp.995-999, 2013.

N. W. Gale, S. Kaplan, E. J. Lowenstein, J. Schlessinger, and D. Bar-sagi, Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras, Nature, vol.363, issue.6424, pp.88-92, 1993.

T. P. Garrett, N. M. Mckern, M. Lou, T. C. Elleman, T. E. Adams et al., The Crystal Structure of a Truncated ErbB2 Ectodomain Reveals an Active Conformation, Poised to Interact with Other ErbB Receptors, Mol. Cell, vol.11, issue.2, pp.495-505, 2003.

M. Gassmann, F. Casagranda, D. Orioli, H. Simon, C. Lai et al., Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor, Nature, vol.378, issue.6555, pp.390-394, 1995.

C. Giani, P. Casalini, S. M. Pupa, R. De-vecchi, E. Ardini et al., Increased expression of c-erbB-2 in hormone-dependent breast cancer cells inhibits cell growth and induces differentiation, Oncogene, vol.17, issue.4, pp.425-432, 1998.

K. Gill, J. L. Macdonald-obermann, and L. J. Pike, Epidermal growth factor receptors containing a single tyrosine in their C-terminal tail bind different effector molecules and are signaling-competent, J. Biol. Chem, vol.292, issue.50, pp.20744-20755, 2017.

A. L. Goldin, Mechanisms of sodium channel inactivation, Curr. Opin. Neurobiol, vol.13, issue.3, pp.284-290, 2003.

N. Gotoh, A. Tojo, M. Hino, Y. Yazaki, and M. Shibuya, A highly conserved tyrosine residue at codon 845 within the kinase domain is not required for the transforming activity of human epidermal growth factor receptor, Biochem. Biophys. Res. Commun, vol.186, issue.2, pp.768-774, 1992.

N. Goudreau, F. Cornille, M. Duchesne, F. Parker, B. Tocque et al., NMR structure of the N-terminal SH3 domain of GRB2 and its complex with a proline-rich peptide from Sos, Nat Struct Biol, vol.1, issue.12, pp.898-907, 1994.

D. Graus-porta, R. R. Beerli, J. M. Daly, and N. E. Hynes, ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling, EMBO J, vol.16, pp.1647-1655, 1997.

B. Gril, M. Vidal, F. Assayag, M. Poupon, W. Liu et al., Grb2-SH3 ligand inhibits the growth of HER2+ cancer cells and has antitumor effects in human cancer xenografts alone and in combination with docetaxel, Int. J. Cancer, vol.121, issue.2, pp.407-415, 2007.
URL : https://hal.archives-ouvertes.fr/inserm-00168667

H. Gu and B. G. Neel, The "Gab" in signal transduction, Trends Cell Biol, vol.13, issue.3, pp.122-130, 2003.

J. P. Guilloteau, N. Fromage, M. Ries-kautt, S. Reboul, D. Bocquet et al., Purification, stabilization, and crystallization of a modular protein: Grb2, Proteins, vol.25, issue.1, pp.112-121, 1996.

J. Habchi, P. Tompa, S. Longhi, and V. N. Uversky, Introducing protein intrinsic disorder, 2014.

B. Halle and M. Davidovic, Biomolecular hydration: From water dynamics to hydrodynamics, Proc. Natl. Acad. Sci, vol.100, issue.21, pp.12135-12140, 2003.

M. Harkiolaki, T. Tsirka, M. Lewitzky, P. C. Simister, D. Joshi et al., Distinct Binding Modes of Two Epitopes in Gab2 that Interact with the SH3C Domain of Grb2, Structure, vol.17, issue.6, pp.809-822, 2009.

R. Hazan, B. Margolis, M. Dombalagian, A. Ullrich, A. Zilberstein et al., Identification of autophosphorylation sites of HER2/neu, Cell Growth Differ, vol.1, issue.1, pp.3-7, 1990.

I. Hellström, G. Goodman, J. Pullman, Y. Yang, and K. E. Hellström, Overexpression of HER-2 in ovarian carcinomas, Cancer Res, vol.61, issue.6, pp.2420-2423, 2001.

J. E. Hinshaw, Dynamin and its role in membrane fission, Annu. Rev. Cell Dev. Biol, vol.16, pp.483-519, 2000.

T. Holbro, R. R. Beerli, F. Maurer, M. Koziczak, C. F. Barbas et al., The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation, Proc. Natl. Acad. Sci, vol.100, issue.15, pp.8933-8938, 2003.

C. Hoppmann, A. Wong, B. Yang, S. Li, T. Hunter et al., Site-specific incorporation of phosphotyrosine using an expanded genetic code, Nat. Chem. Biol, vol.13, issue.8, pp.842-844, 2017.

T. Horan, J. Wen, T. Arakawa, N. Liu, D. Brankow et al., Binding of Neu Differentiation Factor with the Extracellular Domain of Her2 and Her3, J. Biol. Chem, vol.270, issue.41, pp.24604-24608, 1995.

J. Huang and A. D. Mackerell, Force field development and simulations of intrinsically disordered proteins, Curr. Opin. Struct. Biol, vol.48, pp.40-48, 2018.

Y. Huang and Z. Liu, Kinetic Advantage of Intrinsically Disordered Proteins in Coupled Folding-Binding Process: A Critical Assessment of the "Fly-Casting, Mechanism. J. Mol. Biol, vol.393, issue.5, pp.1143-1159, 2009.

S. R. Hubbard, Structural analysis of receptor tyrosine kinases, Prog. Biophys. Mol. Biol, vol.71, issue.3-4, pp.343-358, 1999.

S. R. Hubbard, Juxtamembrane autoinhibition in receptor tyrosine kinases, Nat. Rev. Mol. Cell Biol, vol.5, issue.6, pp.464-471, 2004.

T. Hunter, Tyrosine phosphorylation: thirty years and counting, Curr. Opin. Cell Biol, vol.21, issue.2, pp.140-146, 2009.

T. Hunter and B. M. Sefton, Transforming gene product of Rous sarcoma virus phosphorylates tyrosine, Proc. Natl. Acad. Sci. U. S. A, vol.77, issue.3, pp.1311-1316, 1980.

L. M. Iakoucheva, C. J. Brown, J. Lawson, Z. Obradovi?, and A. Dunker, Intrinsic Disorder in Cell-signaling and Cancer-associated Proteins, J. Mol. Biol, vol.323, issue.3, pp.573-584, 2002.

L. M. Iakoucheva, P. Radivojac, C. J. Brown, T. R. O'connor, J. G. Sikes et al., The importance of intrinsic disorder for protein phosphorylation, Nucleic Acids Res, vol.32, issue.3, pp.1037-1049, 2004.

T. Ishikawa, M. Seto, H. Banno, Y. Kawakita, M. Oorui et al., Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a pyrrolo[3,2-d]pyrimidine scaffold, J. Med. Chem, vol.54, issue.23, pp.8030-8050, 2011.

M. Ivancic, R. J. Daly, and B. A. Lyons, Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2, J. Biomol. NMR, vol.27, issue.3, pp.205-224, 2003.

Y. Iwakura and H. Nawa, ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: pathological implications in schizophrenia and Parkinson's disease. Front, Cell. Neurosci, vol.7, p.4, 2013.

M. R. Jensen, G. Communie, E. A. Ribeiro, N. Martinez, A. Desfosses et al., Intrinsic disorder in measles virus nucleocapsids, Proc. Natl. Acad. Sci, vol.108, issue.24, pp.9839-9844, 2011.

M. R. Jensen, P. R. Markwick, S. Meier, C. Griesinger, M. Zweckstetter et al., Quantitative Determination of the Conformational Properties of Partially Folded and Intrinsically Disordered Proteins Using NMR Dipolar Couplings, Structure, vol.17, issue.9, pp.1169-1185, 2009.

M. Jeon, J. Lee, S. Nam, I. Shin, J. Lee et al., Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells, Exp. Cell Res, vol.333, issue.1, pp.116-126, 2015.

N. Jura, N. F. Endres, K. Engel, S. Deindl, R. Das et al., Mechanism for Activation of the EGF Receptor Catalytic Domain by the Juxtamembrane Segment, Cell, vol.137, issue.7, pp.1293-1307, 2009.

T. Kaneko, The SH3 domain-a family of versatile peptide-and protein-recognition module, Front. Biosci, issue.13, p.4938, 2008.

M. Karplus, Contact Electron-Spin Coupling of Nuclear Magnetic Moments, J. Chem. Phys, vol.30, issue.1, pp.11-15, 1959.

F. Karush, Heterogeneity of the Binding Sites of Bovine Serum Albumin, J. Am. Chem. Soc, vol.72, issue.6, pp.2705-2713, 1950.

K. Kasahara, H. Terazawa, T. Takahashi, and J. Higo, Studies on Molecular Dynamics of Intrinsically Disordered Proteins and Their Fuzzy Complexes: A Mini-Review, Comput. Struct. Biotechnol. J, vol.17, pp.712-720, 2019.

J. C. Kendrew, G. Bodo, H. M. Dintzis, R. G. Parrish, H. Wyckoff et al., A threedimensional model of the myoglobin molecule obtained by x-ray analysis, Nature, vol.181, issue.4610, pp.662-666, 1958.

T. R. Keppel, K. Sarpong, E. M. Murray, J. Monsey, J. Zhu et al., Biophysical evidence for intrinsic disorder in the C-terminal tails of the epidermal growth factor receptor (EGFR) and HER3 receptor tyrosine kinases, J. Biol. Chem, vol.292, issue.2, pp.597-610, 2017.

P. Khanal, G. M. Namgoong, B. S. Kang, E. Woo, and H. S. Choi, The prolyl isomerase Pin1 enhances HER-2 expression and cellular transformation via its interaction with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1, Mol. Cancer Ther, vol.9, issue.3, pp.606-622, 2010.

G. A. Khoury, R. C. Baliban, and C. A. Floudas, Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database, Sci. Rep, vol.1, issue.1, p.90, 2011.

A. G. Kikhney and D. I. Svergun, A practical guide to small angle X-ray scattering (SAXS) of flexible and intrinsically disordered proteins, FEBS Lett, vol.589, issue.19, pp.2570-2577, 2015.

K. L. Kim, D. Kim, S. Lee, S. Kim, J. E. Noh et al., Pairwise detection of site-specific receptor phosphorylations using single-molecule blotting, Nat. Commun, vol.7, issue.1, p.11107, 2016.

M. Kjaergaard and B. B. Kragelund, Functions of intrinsic disorder in transmembrane proteins, Cell. Mol. Life Sci, vol.74, issue.17, pp.3205-3224, 2017.

L. N. Klapper, S. Glathe, N. Vaisman, N. E. Hynes, G. C. Andrews et al., The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors, Proc. Natl. Acad. Sci, vol.96, issue.9, pp.4995-5000, 1999.

D. Kohda, H. Terasawa, S. Ichikawa, K. Ogura, H. Hatanaka et al., Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2, Structure, vol.2, issue.11, pp.1029-1040, 1994.

J. G. Koland, Coarse-Grained Molecular Simulation of Epidermal Growth Factor Receptor Protein Tyrosine Kinase Multi-Site Self-Phosphorylation, PLoS Comput. Biol, vol.10, issue.1, p.1003435, 2014.

P. V. Konarev, V. V. Volkov, A. V. Sokolova, M. H. Koch, and D. I. Svergun, PRIMUS : a Windows PC-based system for small-angle scattering data analysis, J. Appl. Crystallogr, vol.36, issue.5, pp.1277-1282, 2003.

R. Konrat, NMR contributions to structural dynamics studies of intrinsically disordered proteins, J. Magn. Reson, vol.241, issue.1, pp.74-85, 2014.

D. E. Koshland and C. L. Brooks, Application of a Theory of Enzyme Specificity to Protein Synthesis, Proc. Natl. Acad. Sci. U. S. A, vol.44, issue.2, pp.98-104, 1958.

D. E. Koshland, G. Némethy, and D. Filmer, Comparison of Experimental Binding Data and Theoretical Models in Proteins Containing Subunits *, Biochemistry, vol.5, issue.1, pp.365-385, 1966.

S. Kosol, S. Contreras-martos, C. Cedeño, and P. Tompa, Structural characterization of intrinsically disordered proteins by NMR spectroscopy, Molecules, vol.18, issue.9, pp.10802-10828, 2013.

E. Kovacs, R. Das, Q. Wang, T. S. Collier, A. Cantor et al., Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor, Mol. Cell. Biol, vol.35, issue.17, pp.3083-3102, 2015.

E. Kovacs, J. A. Zorn, Y. Huang, T. Barros, and J. Kuriyan, A Structural Perspective on the Regulation of the Epidermal Growth Factor Receptor, Annu. Rev. Biochem, vol.84, issue.1, pp.739-764, 2015.

M. Krzeminski, J. A. Marsh, C. Neale, W. Y. Choy, and J. D. Forman-kay, Characterization of disordered proteins with ENSEMBLE, Bioinformatics, vol.29, issue.3, pp.398-399, 2013.

D. Kumar, N. Sharma, and R. Giri, Therapeutic Interventions of Cancers Using Intrinsically Disordered Proteins as Drug Targets: c-Myc as Model System, Cancer Inform, vol.16, p.117693511769940, 2017.

P. B. Lam, L. N. Burga, B. P. Wu, E. W. Hofstatter, K. P. Lu et al., Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability, Mol. Cancer, vol.7, p.91, 2008.

I. Landrieu, L. Lacosse, A. Leroy, J. M. Wieruszeski, X. Trivelli et al., NMR analysis of a Tau phosphorylation pattern, J. Am. Chem. Soc, vol.128, issue.11, pp.3575-3583, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00085610

S. M. Larson, A. R. Davidson, and A. R. Davidson, The identification of conserved interactions within the SH3 domain by alignment of sequences and structures, Protein Sci, vol.9, issue.11, pp.2170-2180, 2000.

M. Lebendiker and T. Danieli, Production of prone-to-aggregate proteins, FEBS Lett, vol.588, issue.2, pp.236-246, 2014.

S. J. Leblanc, P. Kulkarni, and K. R. Weninger, Single molecule FRET: A powerful tool to study intrinsically disordered proteins, Biomolecules, vol.8, issue.4, 2018.

K. Lee, H. Simon, H. Chen, B. Bates, . Hung et al., Requirement for neuregulin receptor erbB2 in neural and cardiac development, Nature, vol.378, issue.6555, pp.394-398, 1995.

N. Y. Lee, T. L. Hazlett, and J. G. Koland, Structure and dynamics of the epidermal growth factor receptor C-terminal phosphorylation domain, Protein Sci, vol.15, issue.5, pp.1142-1152, 2006.

N. Y. Lee and J. G. Koland, Conformational changes accompany phosphorylation of the epidermal growth factor receptor C-terminal domain, Protein Sci, vol.14, issue.11, pp.2793-803, 2005.

M. A. Lemmon, J. E. Ladbury, V. Mandiyan, M. Zhou, and J. Schlessinger, Independent binding of peptide ligands to the SH2 and SH3 domains of Grb2, J. Biol. Chem, vol.269, issue.50, pp.31653-31658, 1994.

M. A. Lemmon and J. Schlessinger, Cell Signaling by Receptor Tyrosine Kinases, Cell, vol.141, issue.7, pp.1117-1134, 2010.

M. A. Lemmon, J. Schlessinger, and K. M. Ferguson, The EGFR Family: Not So Prototypical Receptor Tyrosine Kinases, Cold Spring Harb. Perspect. Biol, vol.6, issue.4, pp.20768-020768, 2014.

A. E. Lenferink, R. Pinkas-kramarski, M. L. Van-de-poll, M. J. Van-vugt, L. N. Klapper et al., Differential endocytic routing of homo-and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers, EMBO J, vol.17, issue.12, pp.3385-97, 1998.

A. S. Leonard, I. A. Lim, D. E. Hemsworth, M. C. Horne, and J. W. Hell, Calcium/calmodulindependent protein kinase II is associated with the N-methyl-D-aspartate receptor, Proc. Natl. Acad. Sci, vol.96, issue.6, pp.3239-3244, 1999.

E. Lescop, R. Rasia, and B. Brutscher, Hadamard Amino-Acid-Type Edited NMR Experiment for Fast Protein Resonance Assignment, J. Am. Chem. Soc, vol.130, issue.15, pp.5014-5015, 2008.
URL : https://hal.archives-ouvertes.fr/hal-02114814

E. Lescop, P. Schanda, and B. Brutscher, A set of BEST triple-resonance experiments for timeoptimized protein resonance assignment, J. Magn. Reson, vol.187, issue.1, pp.163-169, 2007.
URL : https://hal.archives-ouvertes.fr/hal-02116026

M. Lewitzky, C. Kardinal, N. H. Gehring, E. K. Schmidt, B. Konkol et al., The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif, Oncogene, vol.20, issue.9, pp.1052-1062, 2001.

C. C. Lin, C. Melo, F. A. Ghosh, R. Suen, K. M. Stagg et al., Inhibition of basal FGF receptor signaling by dimeric Grb2, Cell, vol.149, issue.7, pp.1514-1524, 2012.

R. Linding, L. J. Jensen, F. Diella, P. Bork, T. J. Gibson et al., Protein disorder prediction: Implications for structural proteomics, Structure, vol.11, issue.11, pp.1453-1459, 2003.

S. Liokatis, A. Dose, D. Schwarzer, and P. Selenko, Simultaneous Detection of Protein Phosphorylation and Acetylation by High-Resolution NMR Spectroscopy, J. Am. Chem. Soc, vol.132, issue.42, pp.14704-14705, 2010.

B. A. Liu, B. W. Engelmann, and P. D. Nash, The language of SH2 domain interactions defines phosphotyrosine-mediated signal transduction, FEBS Lett, vol.586, issue.17, pp.2597-2605, 2012.

B. A. Liu, E. Shah, K. Jablonowski, A. Stergachis, B. Engelmann et al., The SH2 Domain-Containing Proteins in 21 Species Establish the Provenance and Scope of Phosphotyrosine Signaling in Eukaryotes, Sci. Signal, vol.4, issue.202, pp.83-83, 2011.

J. L. Lopes, A. J. Miles, L. Whitmore, and B. A. Wallace, Distinct circular dichroism spectroscopic signatures of polyproline II and unordered secondary structures: applications in secondary structure analyses, Protein Sci, vol.23, issue.12, pp.1765-72, 2014.

E. J. Lowenstein, R. J. Daly, A. G. Batzer, W. Li, B. Margolis et al., The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling, Cell, vol.70, issue.3, pp.431-442, 1992.

C. Lu, L. Mi, M. J. Grey, J. Zhu, E. Graef et al., Structural Evidence for Loose Linkage between Ligand Binding and Kinase Activation in the Epidermal Growth Factor Receptor, Mol. Cell. Biol, vol.30, issue.22, pp.5432-5443, 2010.

K. P. Lu, Y. Liou, and X. Z. Zhou, Pinning down proline-directed phosphorylation signaling, Trends Cell Biol, vol.12, issue.4, pp.164-172, 2002.

J. L. Macdonald-obermann and L. J. Pike, Different Epidermal Growth Factor (EGF) Receptor Ligands Show Distinct Kinetics and Biased or Partial Agonism for Homodimer and Heterodimer Formation, J. Biol. Chem, vol.289, issue.38, pp.26178-26188, 2014.

J. L. Macdonald-obermann, D. Piwnica-worms, and L. J. Pike, Mechanics of EGF Receptor/ErbB2 kinase activation revealed by luciferase fragment complementation imaging, Proc. Natl. Acad. Sci, vol.109, issue.1, pp.137-142, 2012.

M. J. Macias, S. Wiesner, and M. Sudol, WW and SH3 domains, two different scaffolds to recognize proline-rich ligands, FEBS Lett, vol.513, issue.1, pp.30-37, 2002.

S. Maignan, J. P. Guilloteau, N. Fromage, B. Arnoux, J. Becquart et al., Crystal structure of the mammalian Grb2 adaptor, vol.268, pp.291-293, 1995.

K. A. Majorek, M. L. Kuhn, M. Chruszcz, W. F. Anderson, and W. Minor, Double trouble-Buffer selection and His-tag presence may be responsible for nonreproducibility of biomedical experiments, Protein Sci, vol.23, issue.10, pp.1359-1368, 2014.

G. Manning, The Protein Kinase Complement of the Human Genome. Science (80-. ), vol.298, pp.1912-1934, 2002.

Y. Mansiaux, A. P. Joseph, J. C. Gelly, and A. G. De-brevern, Assignment of polyproline ii conformation and analysis of sequence -structure relationship, PLoS One, vol.6, issue.3, pp.1-15, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00586725

L. E. Marengere, Z. Songyang, G. D. Gish, M. D. Schaller, J. T. Parsons et al., SH2 domain specificity and activity modified by a single residue, Nature, vol.369, issue.6480, pp.502-507, 1994.

B. L. Margolis, I. Lax, R. Kris, M. Dombalagian, A. M. Honegger et al., All autophosphorylation sites of epidermal growth factor (EGF) receptor and HER2/neu are located in their carboxyl-terminal tails. Identification of a novel site in EGF receptor, J. Biol. Chem, vol.264, issue.18, pp.10667-71, 1989.

R. Marone, D. Hess, D. Dankort, W. J. Muller, N. E. Hynes et al., Memo mediates ErbB2-driven cell motility, Nat. Cell Biol, vol.6, issue.6, pp.515-522, 2004.

J. A. Marsh, V. K. Singh, Z. Jia, and J. D. Forman-kay, Sensitivity of secondary structure propensities to sequence differences between alpha-and gamma-synuclein: implications for fibrillation, Protein Sci, vol.15, issue.12, pp.2795-2804, 2006.

M. S. Martinez, A. Nonell-canals, M. Sanchez-martinez, M. S. Martinez, A. Nonell-canals et al., Intrinsically Disordered Proteins as Drug Targets, MOJ Proteomics Bioinforma, vol.5, issue.3, pp.24-26, 2017.

M. Mayzel, J. Rosenlöw, L. Isaksson, and V. Y. Orekhov, Time-resolved multidimensional NMR with non-uniform sampling, J. Biomol. NMR, vol.58, issue.2, pp.129-139, 2014.

C. B. Mcdonald, J. E. Balke, V. Bhat, D. C. Mikles, B. J. Deegan et al., Multivalent Binding and Facilitated Diffusion Account for the Formation of the Grb2-Sos1 Signaling Complex in a Cooperative Manner, Biochemistry, vol.51, issue.10, pp.2122-2135, 2012.

C. B. Mcdonald, V. Bhat, D. C. Mikles, and B. J. Deegan, Bivalent Binding Drives the Formation of Grb2-Gab1 Signaling Complex in a Non-Cooperative Manner, FEBS Lett, vol.279, issue.12, pp.2156-2173, 2012.

C. B. Mcdonald, J. El-hokayem, N. Zafar, J. E. Balke, V. Bhat et al., Allostery mediates ligand binding to Grb2 adaptor in a mutually exclusive manner, J. Mol. Recognit, vol.26, issue.2, pp.92-103, 2013.

C. B. Mcdonald, K. L. Seldeen, B. J. Deegan, V. Bhat, and A. Farooq, Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control, Arch. Biochem. Biophys, vol.494, issue.2, pp.216-241, 2010.

C. B. Mcdonald, K. L. Seldeen, B. J. Deegan, and A. Farooq, Structural basis of the differential binding of the SH3 domains of Grb2 adaptor to the guanine nucleotide exchange factor Sos1, Arch. Biochem. Biophys, vol.479, issue.1, pp.52-62, 2008.

C. B. Mcdonald, K. L. Seldeen, B. J. Deegan, and A. Farooq, SH3 Domains of Grb2 Adaptor Bind to PX?PXR Motifs Within the Sos1 Nucleotide Exchange Factor in a Discriminate Manner, Biochemistry, vol.48, issue.19, pp.4074-4085, 2009.

C. B. Mcdonald, K. L. Seldeen, B. J. Deegan, M. S. Lewis, and A. Farooq, Grb2 adaptor undergoes conformational change upon dimerization, Arch. Biochem. Biophys, vol.475, issue.1, pp.25-35, 2008.

J. M. Mendrola, M. B. Berger, M. C. King, and M. A. Lemmon, The Single Transmembrane Domains of ErbB Receptors Self-associate in Cell Membranes, J. Biol. Chem, vol.277, issue.7, pp.4704-4712, 2002.

A. Meola, C. Deville, S. A. Jeffers, P. Guardado-calvo, I. Vasiliauskaite et al., Robust and low cost uniform< sup> 15</sup> N-labeling of proteins expressed in< i> Drosophila</i> S2 cells and< i> Spodoptera frugiperda</i> Sf9 cells for NMR applications, J. Struct. Biol, vol.188, issue.1, pp.71-78, 2014.

B. Mészáros, G. Erdös, and Z. Dosztányi, IUPred2A: Context-dependent prediction of protein disorder as a function of redox state and protein binding, Nucleic Acids Res, vol.46, issue.W1, pp.329-337, 2018.

S. J. Metallo, Intrinsically disordered proteins are potential drug targets, Curr. Opin. Chem. Biol, vol.14, issue.4, pp.481-488, 2010.

L. Mi, C. Lu, Z. Li, N. Nishida, T. Walz et al., Simultaneous visualization of the extracellular and cytoplasmic domains of the epidermal growth factor receptor, Nat. Struct. Mol. Biol, vol.18, issue.9, pp.984-989, 2011.

S. Milles, N. Salvi, M. Blackledge, and M. R. Jensen, Characterization of intrinsically disordered proteins and their dynamic complexes: From in vitro to cell-like environments, Prog. Nucl. Magn. Reson. Spectrosc, vol.109, pp.79-100, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01995911

Y. Minezaki, K. Homma, and K. Nishikawa, Intrinsically Disordered Regions of Human Plasma Membrane Proteins Preferentially Occur in the Cytoplasmic Segment, J. Mol. Biol, vol.368, issue.3, pp.902-913, 2007.

M. Miskei, C. Antal, and M. Fuxreiter, FuzDB: Database of fuzzy complexes, a tool to develop stochastic structure-function relationships for protein complexes and higher-order assemblies, Nucleic Acids Res, vol.45, issue.D1, pp.228-235, 2017.

J. Monod and F. Jacob, Teleonomic mechanisms in cellular metabolism, growth, and differentiation, Cold Spring Harb. Symp. Quant. Biol, vol.26, pp.389-401, 1961.

J. Monod, J. Wyman, and J. Changeux, On the nature of allosteric transitions: A plausible model, J. Mol. Biol, vol.12, issue.1, pp.88-118, 1965.

J. Monsey, W. Shen, P. Schlesinger, and R. Bose, Her4 and Her2/neu tyrosine kinase domains dimerize and activate in a reconstituted in vitro system, J. Biol. Chem, vol.285, issue.10, pp.7035-7044, 2010.

T. Moriki, H. Maruyama, and I. N. Maruyama, Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain, J. Mol. Biol, vol.311, issue.5, pp.1011-1026, 2001.

H. N. Motlagh, J. O. Wrabl, J. Li, and V. J. Hilser, The ensemble nature of allostery, Nature, vol.508, issue.7496, pp.331-339, 2014.

A. Musacchio, How SH3 domains recognize proline, Adv. Protein Chem, vol.61, pp.211-268, 2002.

M. Mustafa, A. Mirza, and N. Kannan, Conformational regulation of the EGFR kinase core by the juxtamembrane and C-terminal tail: A molecular dynamics study, Proteins Struct. Funct. Bioinforma, vol.79, issue.1, pp.99-114, 2011.

A. Mylona, F. Theillet, C. Foster, T. M. Cheng, F. Miralles et al., Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation, Science, vol.354, issue.6309, pp.233-237, 2016.

R. Nahta and F. J. Esteva, Trastuzumab: triumphs and tribulations, Oncogene, vol.26, issue.25, pp.3637-3643, 2007.

A. Nakata, J. I. Miyagawa, S. Yamashita, M. Nishida, R. Tamura et al., Localization of heparin-binding epidermal growth factor-like growth factor in human coronary arteries: Possible roles of HB-EGF in the formation of coronary atherosclerosis, Circulation, vol.94, issue.11, pp.2778-2786, 1996.

B. Nami, H. Maadi, W. , and Z. , Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in Targeting HER2-Positive Breast Cancer, Cancers (Basel), vol.10, issue.10, p.342, 2018.

T. J. Narwani, H. Santuz, N. Shinada, A. Melarkode-vattekatte, Y. Ghouzam et al., Recent advances on polyproline II, vol.49, pp.705-713, 2017.
URL : https://hal.archives-ouvertes.fr/inserm-01573940

I. Nasir, P. L. Onuchic, S. R. Labra, and A. A. Deniz, Single-molecule fluorescence studies of intrinsically disordered proteins and liquid phase separation, Biochim. Biophys. Acta -Proteins Proteomics, vol.1867, issue.10, pp.980-987, 2019.

M. H. Nelson and C. R. Dolder, Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors, Ann. Pharmacother, vol.40, issue.2, pp.261-270, 2006.

P. Nioche, W. Liu, I. Broutin, F. Charbonnier, M. Latreille et al., Crystal structures of the SH2 domain of grb2: highlight on the binding of a new high-affinity inhibitor, J. Mol. Biol, vol.315, issue.5, pp.1167-1177, 2002.

G. Nodet, L. Salmon, V. Ozenne, S. Meier, M. R. Jensen et al., Quantitative description of backbone conformational sampling of unfolded proteins at amino acid resolution from NMR residual dipolar couplings, J. Am. Chem. Soc, vol.131, issue.49, pp.17908-17918, 2009.
URL : https://hal.archives-ouvertes.fr/hal-01696459

M. E. Oates, P. Romero, T. Ishida, M. Ghalwash, M. J. Mizianty et al., D2P2: database of disordered protein predictions, Nucleic Acids Res, issue.1, p.41, 2013.

D. P. Obrien, B. Hernandez, D. Durand, V. Hourdel, A. C. Sotomayor-pérez et al., Structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion, Sci. Rep, vol.5, pp.1-11, 2015.
URL : https://hal.archives-ouvertes.fr/pasteur-01406897

H. Ogiso, R. Ishitani, O. Nureki, S. Fukai, M. Yamanaka et al., Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains, Cell, vol.110, issue.6, pp.775-787, 2002.

K. Ogura and H. Okamura, Conformational change of Sos-derived proline-rich peptide upon binding Grb2 N-terminal SH3 domain probed by NMR, Sci. Rep, vol.3, issue.1, p.2913, 2013.

E. O&apos;keefe, M. D. Hollenberg, and P. Cuatrecasas, Epidermal growth factor. Characteristics of specific binding in membranes from liver, placenta, and other target tissues, Arch. Biochem. Biophys, vol.164, issue.2, pp.518-526, 1974.

C. J. Oldfield, Y. Cheng, M. S. Cortese, P. Romero, V. N. Uversky et al., Coupled Folding and Binding with ?-Helix-Forming Molecular Recognition Elements, Biochemistry, vol.44, issue.37, pp.12454-12470, 2005.

J. G. Olsen, K. Teilum, and B. B. Kragelund, Behaviour of intrinsically disordered proteins in protein-protein complexes with an emphasis on fuzziness, Cell. Mol. Life Sci, vol.74, issue.17, pp.3175-3183, 2017.

V. Ozenne, F. Bauer, L. Salmon, J. Huang, M. R. Jensen et al., Flexible-meccano: a tool for the generation of explicit ensemble descriptions of intrinsically disordered proteins and their associated experimental observables, Bioinformatics, vol.28, issue.11, pp.1463-1470, 2012.

K. E. Paleologou, A. Oueslati, G. Shakked, C. C. Rospigliosi, H. Kim et al., Phosphorylation at S87 Is Enhanced in Synucleinopathies, Inhibits -Synuclein Oligomerization, and Influences Synuclein-Membrane Interactions, J. Neurosci, vol.30, issue.9, pp.3184-3198, 2010.

A. Panek, O. Pietrow, P. Filipkowski, and J. Synowiecki, Effects of the polyhistidine tag on kinetics and other properties of trehalose synthase from Deinococcus geothermalis, Acta Biochim. Pol, vol.60, issue.2, pp.163-169, 2013.

D. Papaioannou, S. Geibel, M. B. Kunze, C. W. Kay, and G. Waksman, Structural and biophysical investigation of the interaction of a mutant Grb2 SH2 domain (W121G) with its cognate phosphopeptide, Protein Sci, vol.25, issue.3, pp.627-637, 2016.

H. Park, M. J. Hohn, T. Umehara, L. Guo, E. M. Osborne et al., Expanding the Genetic Code of Escherichia coli with Phosphoserine, Science, vol.333, issue.6046, pp.1151-1154, 2011.

T. Pawson, SH2 and SH3 domains, Curr. Opin. Struct. Biol, vol.2, issue.3, pp.432-437, 1992.

J. S. Pedersen and P. Schurtenberger, Scattering functions of semiflexible polymers with and without excluded volume effects, Macromolecules, vol.29, issue.23, pp.7602-7612, 1996.

E. Penuel, R. W. Akita, and M. X. Sliwkowski, Identification of a Region within the ErbB2/HER2 Intracellular Domain That Is Necessary for Ligand-independent Association, J. Biol. Chem, vol.277, issue.32, pp.28468-28473, 2002.

J. Pérez and P. Vachette, A Successful Combination: Coupling SE-HPLC with SAXS, Adv. Exp. Med. Biol, vol.1009, pp.183-199, 2017.

J. Pérez, P. Vachette, D. Russo, M. Desmadril, D. et al., Heat-induced unfolding of neocarzinostatin, a small all-? protein investigated by small-angle X-ray scattering 1 1Edited by M. F. Moody, J. Mol. Biol, vol.308, issue.4, pp.721-743, 2001.

K. Pervushin, R. Riek, G. Wider, and K. Wüthrich, Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution, Proc. Natl. Acad. Sci. U. S. A, vol.94, issue.23, pp.12366-71, 1997.

G. Pines, P. H. Huang, Y. Zwang, F. M. White, Y. et al., EGFRvIV: A previously uncharacterized oncogenic mutant reveals a kinase autoinhibitory mechanism, Oncogene, vol.29, issue.43, pp.5850-5860, 2010.

R. Pinkas-kramarski, L. Soussan, H. Waterman, G. Levkowitz, I. Alroy et al., Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions, EMBO J, vol.15, issue.10, pp.2452-2467, 1996.

F. Poy, M. B. Yaffe, J. Sayos, K. Saxena, M. Morra et al., Crystal Structures of the XLP Protein SAP Reveal a Class of SH2 Domains with Extended, Phosphotyrosine-Independent Sequence Recognition, Mol. Cell, vol.4, issue.4, pp.555-561, 1999.

M. F. Press, M. C. Pike, V. R. Chazin, G. Hung, J. A. Udove et al., Her-2/neu Expression in Nodenegative Breast Cancer: Direct Tissue Quantitation by Computerized Image Analysis and Association of Overexpression with Increased Risk of Recurrent Disease, Cancer Res, vol.53, issue.20, pp.4960-4970, 1993.

C. Przybylski, M. A. Jünger, J. Aubertin, F. Radvanyi, R. Aebersold et al., Quantitative analysis of protein complex constituents and their phosphorylation states on a LTQ-orbitrap instrument, J. Proteome Res, vol.9, issue.10, pp.5118-5132, 2010.

E. Purba, E. Saita, and I. Maruyama, Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The "Rotation Model, Cells, vol.6, issue.2, p.13, 2017.

X. Qian, C. M. Levea, J. K. Freeman, W. C. Dougall, and M. I. Greene, Heterodimerization of epidermal growth factor receptor and wild-type or kinase-deficient Neu: a mechanism of interreceptor kinase activation and transphosphorylation, Proc. Natl. Acad. Sci, vol.91, issue.4, pp.1500-1504, 1994.

B. Y. Qin, C. Liu, H. Srinath, S. S. Lam, J. J. Correia et al., Crystal structure of IRF-3 in complex with CBP, Structure, vol.13, issue.9, pp.1269-77, 2005.

C. Qiu, S. Lienhard, N. E. Hynes, A. Badache, and D. J. Leahy, Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an ErbB2-derived Phosphopeptide in Its Vestigial Active Site, J. Biol. Chem, vol.283, issue.5, pp.2734-2740, 2008.

J. Rahuel, B. Gay, D. Erdmann, A. Strauss, C. Garcia-echeverria et al., Structural basis for specificity of GRB2-SH2 revealed by a novel ligand binding mode, Nat. Struct Biol, vol.3, issue.7, pp.586-589, 1996.

R. Ranganathan, K. P. Lu, T. Hunter, and J. P. Noel, Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent, Cell, vol.89, issue.6, pp.875-86, 1997.

K. S. Ravichandran, U. Lorenz, S. E. Shoelson, and S. J. Burakoff, Interaction of Shc with Grb2 regulates association of Grb2 with mSOS, Mol. Cell. Biol, vol.15, issue.2, pp.593-600, 1995.

T. Ravid, J. M. Heidinger, P. Gee, E. M. Khan, and T. Goldkorn, c-Cbl-mediated Ubiquitinylation Is Required for Epidermal Growth Factor Receptor Exit from the Early Endosomes, J. Biol. Chem, vol.279, issue.35, pp.37153-37162, 2004.

V. Receveur-brechot and D. Durand, How Random are Intrinsically Disordered Proteins? A Small Angle Scattering Perspective, Curr. Protein Pept. Sci, vol.13, issue.1, pp.55-75, 2012.

R. Brewer, M. Choi, S. H. Alvarado, D. Moravcevic, K. Pozzi et al., The Juxtamembrane Region of the EGF Receptor Functions as an Activation Domain, Mol. Cell, vol.34, issue.6, pp.641-651, 2009.

U. Reimer, G. Scherer, M. Drewello, S. Kruber, M. Schutkowski et al., Side-chain effects on peptidyl-prolyl cis/trans isomerisation, J. Mol. Biol, vol.279, issue.2, pp.449-460, 1998.

D. Riethmacher, E. Sonnenberg-riethmacher, V. Brinkmann, T. Yamaai, G. R. Lewin et al., Severe neuropathies in mice with targeted mutations in the ErbB3 receptor, Nature, vol.389, issue.6652, pp.725-730, 1997.

D. R. Robinson, Y. Wu, and S. Lin, The protein tyrosine kinase family of the human genome, Oncogene, vol.19, issue.49, pp.5548-5557, 2000.

J. M. Rogers, C. T. Wong, C. , and J. , Coupled Folding and Binding of the Disordered Protein PUMA Does Not Require Particular Residual Structure, J. Am. Chem. Soc, vol.136, issue.14, pp.5197-5200, 2014.

P. Romero, Z. Obradovic, C. R. Kissinger, J. E. Villafranca, E. Garner et al., Thousands of proteins likely to have long disordered regions, Pac. Symp. Biocomput, pp.437-485, 1998.

G. L. Rosano and E. A. Ceccarelli, Recombinant protein expression in Escherichia coli: advances and challenges, Front. Microbiol, vol.5, pp.1-17, 2014.

J. Rosenlöw, L. Isaksson, M. Mayzel, J. Lengqvist, and V. Y. Orekhov, Tyrosine Phosphorylation within the Intrinsically Disordered Cytosolic Domains of the B-Cell Receptor: An NMR-Based Structural Analysis, PLoS One, vol.9, issue.4, p.96199, 2014.

H. Ruan, Q. Sun, W. Zhang, Y. Liu, L. et al., Targeting intrinsically disordered proteins at the edge of chaos, Drug Discov. Today, vol.24, issue.1, pp.217-227, 2019.

I. Sadowski, J. C. Stone, and T. Pawson, A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps, Mol. Cell. Biol, vol.6, issue.12, pp.4396-408, 1986.

K. Saksela and P. Permi, SH3 domain ligand binding: What's the consensus and where's the specificity?, FEBS Lett, vol.586, issue.17, pp.2609-2614, 2012.

N. Salvi, A. Abyzov, and M. Blackledge, Atomic resolution conformational dynamics of intrinsically disordered proteins from NMR spin relaxation, Prog. Nucl. Magn. Reson. Spectrosc, pp.43-60, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01685061

A. Schechter, M. Hung, L. Vaidyanathan, R. Weinberg, T. Yang-feng et al., The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor, Science, vol.229, issue.4717, pp.976-978, 1985.

A. L. Schechter, D. F. Stern, L. Vaidyanathan, S. J. Decker, J. A. Drebin et al., The neu oncogene: An erb-B-related gene encoding a 185,000-Mr tumour antigen, Nature, issue.5994, pp.513-516, 1984.

N. Schiering, E. Casale, P. Caccia, P. Giordano, and C. Battistini, Dimer Formation through Domain Swapping in the Crystal Structure of the Grb2-SH2-Ac-pYVNV Complex, Biochemistry, vol.39, issue.44, pp.13376-13382, 2000.

W. X. Schulze, L. Deng, and M. Mann, Phosphotyrosine interactome of the ErbB-receptor kinase family, Mol. Syst. Biol, vol.1, issue.1, pp.1-13, 2005.

H. Schwalbe, K. M. Fiebig, M. Buck, J. A. Jones, S. B. Grimshaw et al., Structural and Dynamical Properties of a Denatured Protein, Heteronuclear 3D NMR Experiments and Theoretical Simulations of Lysozyme in 8 M Urea, vol.36, pp.8977-8991, 1997.

N. Sciolino, D. S. Burz, and A. Shekhtman, Cell NMR Spectroscopy of Intrinsically Disordered Proteins. Proteomics, vol.19, issue.6, p.1800055, 2019.

J. Sebastian, R. G. Richards, M. P. Walker, J. F. Wiesen, Z. Werb et al., Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis, Cell Growth Differ, vol.9, issue.9, pp.777-85, 1998.

O. Segatto, F. Lonardo, J. H. Pierce, D. P. Bottaro, D. Fiore et al., The role of autophosphorylation in modulation of erbB-2 transforming function, New Biol, vol.2, issue.2, pp.187-95, 1990.

P. Selenko, D. P. Frueh, S. J. Elsaesser, W. Haas, S. P. Gygi et al., In situ observation of protein phosphorylation by high-resolution NMR spectroscopy, Nat. Struct. Mol. Biol, vol.15, issue.3, pp.321-329, 2008.

M. M. Senior, A. F. Frederick, S. Black, N. J. Murgolo, L. M. Perkins et al., The three-dimensional solution structure of the Src homology domain-2 of the growth factor receptor-bound protein-2, J. Biomol. NMR, vol.11, issue.2, pp.153-164, 1998.

P. Sharp and V. A. Bloomfield, Light scattering from wormlike chains with excluded volume effects, Biopolymers, vol.6, issue.8, pp.1201-1211, 1968.

S. Sharpe, K. R. Barber, and C. W. Grant, Evidence of a Tendency to Self-Association of the Transmembrane Domain of ErbB-2 in Fluid Phospholipid Bilayers, Biochemistry, vol.41, issue.7, pp.2341-2352, 2002.

Y. Shen and A. Bax, Prediction of Xaa-Pro peptide bond conformation from sequence and chemical shifts, J. Biomol. NMR, vol.46, issue.3, pp.199-204, 2010.

Y. Shen, F. Delaglio, G. Cornilescu, and A. Bax, TALOS+: A hybrid method for predicting protein backbone torsion angles from NMR chemical shifts, J. Biomol. NMR, vol.44, issue.4, pp.213-236, 2009.

Y. Shen, J. Roche, A. Grishaev, and A. Bax, Prediction of nearest neighbor effects on backbone torsion angles and NMR scalar coupling constants in disordered proteins, Protein Sci, vol.27, issue.1, pp.146-158, 2018.

A. Shrestha, G. Hamilton, E. O&apos;neill, S. Knapp, and J. M. Elkins, Analysis of conditions affecting auto-phosphorylation of human kinases during expression in bacteria, Protein Expr. Purif, vol.81, issue.1, pp.136-143, 2012.

N. Sibille and P. Bernadó, Structural characterization of intrinsically disordered proteins by the combined use of NMR and SAXS, Biochem. Soc. Trans, vol.40, issue.5, pp.955-962, 2012.
URL : https://hal.archives-ouvertes.fr/hal-02347934

D. J. Slamon, G. M. Clark, S. G. Wong, W. J. Levin, A. Ullrich et al., Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene, Science, vol.235, issue.4785, pp.177-82, 1987.

L. J. Smith, K. A. Bolin, H. Schwalbe, M. W. Macarthur, J. M. Thornton et al., Analysis of main chain torsion angles in proteins: prediction of NMR coupling constants for native and random coil conformations, J. Mol. Biol, vol.255, issue.3, pp.494-506, 1996.

Z. Sólyom, P. Ma, M. Schwarten, M. Bosco, A. Polidori et al., The Disordered Region of the HCV Protein NS5A: Conformational Dynamics, SH3 Binding, and Phosphorylation, Biophys. J, vol.109, issue.7, pp.1483-1496, 2015.

J. Song, L. Guo, H. Muradov, N. O. Artemyev, A. E. Ruoho et al., Intrinsically disordered -subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure, Proc. Natl. Acad. Sci, vol.105, issue.5, pp.1505-1510, 2008.

A. Sorkin and L. K. Goh, Endocytosis and intracellular trafficking of ErbBs, Exp. Cell Res, vol.315, issue.4, pp.683-696, 2009.

A. Sorkin, K. Helin, C. M. Waters, G. Carpenter, and L. Beguinot, Multiple autophosphorylation sites of the epidermal growth factor receptor are essential for receptor kinase activity and internalization. Contrasting significance of tyrosine 992 in the native and truncated receptors, J. Biol. Chem, vol.267, issue.12, pp.8672-8680, 1992.

G. Sriram and R. B. Birge, Commentary: The carboxyl-terminal Crk SH3 domain: Regulatory strategies and new perspectives, FEBS Lett, vol.586, issue.17, pp.2615-2618, 2012.

J. Stamos, M. X. Sliwkowski, and C. Eigenbrot, Structure of the Epidermal Growth Factor Receptor Kinase Domain Alone and in Complex with a 4-Anilinoquinazoline Inhibitor, J. Biol. Chem, vol.277, issue.48, pp.46265-46272, 2002.

D. Stein, J. Wu, S. Fuqua, C. Roonprapunt, V. Yajnik et al., The SH2 domain protein GRB-7 is co-amplified, overexpressed and in a tight complex with HER2 in breast cancer, EMBO J, vol.13, issue.6, pp.1331-1340, 1994.

R. A. Stein and J. V. Staros, Insights into the evolution of the ErbB receptor family and their ligands from sequence analysis, BMC Evol. Biol, vol.6, pp.1-17, 2006.

S. Strack and R. J. Colbran, Autophosphorylation-dependent Targeting of Calcium/ Calmodulindependent Protein Kinase II by the NR2B Subunit of the N -Methyl-d-aspartate Receptor, J. Biol. Chem, vol.273, issue.33, pp.20689-20692, 1998.

J. Su, L. Yang, and J. Sap, Association between Receptor Protein-Tyrosine Phosphatase RPTPa and the Grb2 Adaptor, J. Biol. Chem, vol.271, issue.45, pp.28086-28096, 1996.

D. Svergun, C. Barberato, and M. H. Koch, CRYSOL -A program to evaluate X-ray solution scattering of biological macromolecules from atomic coordinates, J. Appl. Crystallogr, vol.28, issue.6, pp.768-773, 1995.

D. I. Svergun, Determination of the regularization parameter in indirect-transform methods using perceptual criteria, J. Appl. Crystallogr, vol.25, issue.4, pp.495-503, 1992.

S. M. Swain, J. Baselga, S. Kim, J. Ro, V. Semiglazov et al., Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer, vol.372, pp.724-734, 2015.

R. Tao and I. N. Maruyama, All EGF(ErbB) receptors have preformed homo-and heterodimeric structures in living cells, J. Cell Sci, vol.121, issue.19, pp.3207-3217, 2008.

F. Theillet, A. Binolfi, B. Bekei, A. Martorana, H. M. Rose et al., Structural disorder of monomeric ?-synuclein persists in mammalian cells, Nature, vol.530, issue.7588, pp.45-50, 2016.

F. Theillet, A. Binolfi, T. Frembgen-kesner, K. Hingorani, M. Sarkar et al., Physicochemical Properties of Cells and Their Effects on Intrinsically Disordered Proteins (IDPs), Chem. Rev, vol.114, issue.13, pp.6661-6714, 2014.

F. Theillet, C. Smet-nocca, S. Liokatis, R. Thongwichian, J. Kosten et al., Cell signaling, post-translational protein modifications and NMR spectroscopy, J. Biomol. NMR, vol.54, issue.3, pp.217-236, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00765863

K. W. Thiel and G. Carpenter, Epidermal growth factor receptor juxtamembrane region regulates allosteric tyrosine kinase activation, Proc. Natl. Acad. Sci, vol.104, issue.49, pp.19238-19243, 2007.

M. C. Thielges, J. K. Chung, J. Y. Axup, and M. D. Fayer, Influence of Histidine Tag Attachment on Picosecond Protein Dynamics, Biochemistry, vol.50, issue.25, pp.5799-5805, 2011.

T. E. Thingholm, O. N. Jensen, and M. R. Larsen, Analytical strategies for phosphoproteomics, Proteomics, vol.9, issue.6, pp.1451-1468, 2009.

K. H. Thornton, W. T. Mueller, P. Mcconnell, G. Zhu, A. R. Saltiel et al., Nuclear magnetic resonance solution structure of the growth factor receptor-bound protein 2 Src homology 2 domain, Biochemistry, vol.35, issue.36, pp.11852-11864, 1996.

P. E. Thorsness and D. E. Koshland, Inactivation of isocitrate dehydrogenase by phosphorylation is mediated by the negative charge of the phosphate, J. Biol. Chem, vol.262, issue.22, pp.10422-10427, 1987.

P. Tompa, Multisteric Regulation by Structural Disorder in Modular Signaling Proteins: An Extension of the Concept of Allostery, Chem. Rev, vol.114, issue.13, pp.6715-6732, 2014.

P. Tompa and M. Fuxreiter, Fuzzy complexes: polymorphism and structural disorder in proteinprotein interactions, Trends Biochem. Sci, vol.33, issue.1, pp.2-8, 2008.

G. Tria, H. D. Mertens, M. Kachala, and D. I. Svergun, Advanced ensemble modelling of flexible macromolecules using X-ray solution scattering, IUCrJ, vol.2, issue.2, pp.207-217, 2015.

E. Tzahar, H. Waterman, X. Chen, G. Levkowitz, D. Karunagaran et al., A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor, Mol. Cell. Biol, vol.16, issue.10, pp.5276-5287, 1996.

K. Ugocsai, L. Mándoky, L. Tiszlavicz, and J. Molnár, Investigation of HER2 overexpression in non-small cell lung cancer, Anticancer Res, vol.25, issue.4, pp.3061-3067, 2005.

A. Urbanek, A. Morató, F. Allemand, E. Delaforge, A. Fournet et al., A General Strategy to Access Structural Information at Atomic Resolution in Polyglutamine Homorepeats, Angew. Chemie -Int. Ed, vol.57, issue.14, pp.3598-3601, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01737188

V. N. Uversky, Natively unfolded proteins: A point where biology waits for physics, Protein Sci, vol.11, issue.4, pp.739-756, 2002.

V. N. Uversky, Targeting intrinsically disordered proteins in neurodegenerative and protein dysfunction diseases: another illustration of the D 2 concept, Expert Rev. Proteomics, vol.7, issue.4, pp.543-564, 2010.

V. N. Uversky, Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators, Front. Mol. Biosci, vol.1, pp.1-24, 2014.

V. N. Uversky, Intrinsically disordered proteins and their (disordered) proteomes in neurodegenerative disorders, Front. Aging Neurosci, vol.7, pp.1-6, 2015.

V. N. Uversky, Intrinsic Disorder, Protein-Protein Interactions, and Disease, 2017.

V. N. Uversky, Protein intrinsic disorder-based liquid-liquid phase transitions in biological systems: Complex coacervates and membrane-less organelles, Adv. Colloid Interface Sci, vol.239, pp.97-114, 2017.

V. N. Uversky, J. R. Gillespie, and A. L. Fink, Why are "natively unfolded" proteins unstructured under physiologic conditions?, Proteins Struct. Funct. Genet, vol.41, issue.3, pp.415-427, 2000.

V. N. Uversky, C. J. Oldfield, and A. K. Dunker, Showing your ID: Intrinsic disorder as an ID for recognition, regulation and cell signaling, 2005.

M. Valius and A. Kazlauskas, Phospholipase C-?1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal, Cell, vol.73, issue.2, pp.321-334, 1993.

R. Van-der-lee, M. Buljan, B. Lang, R. J. Weatheritt, G. W. Daughdrill et al., Classification of intrinsically disordered regions and proteins, Chem. Rev, vol.114, issue.13, pp.6589-6631, 2014.

A. Vaskovsky, Z. Lupowitz, S. Erlich, and R. Pinkas-kramarski, ErbB-4 Activation Promotes Neurite Outgrowth in PC12 Cells, J. Neurochem, vol.74, issue.3, pp.979-987, 2000.

M. Vidal, N. Goudreau, F. Cornille, D. Cussac, E. Gincel et al., Molecular and cellular analysis of Grb2 SH3 domain mutants: Interaction with Sos and dynamin, J. Mol. Biol, vol.290, issue.3, pp.717-730, 1999.

W. F. Vranken, W. Boucher, T. J. Stevens, R. H. Fogh, A. Pajon et al., The CCPN data model for NMR spectroscopy: Development of a software pipeline, Proteins, vol.59, issue.4, pp.687-696, 2005.

G. W. Vuister and A. Bax, Quantitative J Correlation -a New Approach for Measuring Homonuclear 3-Bond J(H(N)H(Alpha)) Coupling-Constants in N-15-Enriched Proteins, J. Am. Chem. Soc, vol.115, issue.17, pp.7772-7777, 1993.

M. J. Wagner, M. M. Stacey, B. A. Liu, and T. Pawson, Molecular mechanisms of SH2-and PTB-Domain-containing proteins in receptor tyrosine kinase signaling, Cold Spring Harb. Perspect. Biol, vol.5, issue.12, 2013.

G. M. Walton, W. S. Chen, M. G. Rosenfeld, and G. N. Gill, Analysis of deletions of the carboxyl terminus of the epidermal growth factor receptor reveals self-phosphorylation at tyrosine 992 and enhanced in vivo tyrosine phosphorylation of cell substrates, J. Biol. Chem, vol.265, issue.3, pp.1750-1754, 1990.

Y. Wang, L. Pinet, N. Assrir, L. Elantak, F. Guerlesquin et al., 1H, 13C and 15N assignments of the C-terminal intrinsically disordered cytosolic fragment of the receptor tyrosine kinase ErbB2, Biomol. NMR Assign, vol.12, issue.1, pp.23-26, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01792618

J. J. Ward, J. S. Sodhi, L. J. Mcguffin, B. F. Buxton, and D. T. Jones, Prediction and Functional Analysis of Native Disorder in Proteins from the Three Kingdoms of Life, J. Mol. Biol, vol.337, issue.3, pp.635-645, 2004.

M. D. Ward and D. J. Leahy, Kinase Activator-Receiver Preference in ErbB Heterodimers Is Determined by Intracellular Regions and Is Not Coupled to Extracellular Asymmetry, J. Biol. Chem, vol.290, issue.3, pp.1570-1579, 2015.

L. Waters, B. Yue, V. Veverka, P. Renshaw, J. Bramham et al., Structural diversity in p160/CREB-binding protein coactivator complexes, J. Biol. Chem, vol.281, issue.21, pp.14787-95, 2006.

D. K. Wilkins, S. B. Grimshaw, V. Receveur, C. M. Dobson, J. A. Jones et al., Hydrodynamic Radii of Native and Denatured Proteins Measured by Pulse Field Gradient NMR Techniques, Biochemistry, vol.38, issue.50, pp.16424-16431, 1999.

K. J. Wilson, C. Mill, S. Lambert, J. Buchman, T. R. Wilson et al., EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling, Growth Factors, vol.30, issue.2, pp.107-116, 2012.

D. S. Wishart and B. D. Sykes, Chemical shifts as a tool for structure determination, Methods Enzymol, vol.239, pp.363-92, 1982.

M. Wittekind, C. Mapelli, B. T. Farmer, K. Suen, V. Goldfarb et al., Orientation of Peptide Fragments from Sos Proteins Bound to the N-Terminal SH3 Domain of Grb2 Determined by NMR Spectroscopy, Biochemistry, vol.33, issue.46, pp.13531-13539, 1994.

M. Wittekind, C. Mapelli, V. Lee, V. Goldfarb, M. S. Friedrichs et al., Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-residue peptide derived from SOS: Direct refinement against NOEs, J-couplings and 1 H and 13 C chemical shifts, J. Mol. Biol, vol.267, issue.4, pp.933-952, 1997.

E. R. Wood, L. M. Shewchuk, B. Ellis, P. Brignola, R. L. Brashear et al., Proc. Natl. Acad. Sci, vol.105, issue.6, pp.2773-2778, 2008.

E. R. Wood, A. T. Truesdale, O. B. Mcdonald, D. Yuan, A. Hassell et al., A Unique Structure for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib), Cancer Res, vol.64, issue.18, pp.6652-6659, 2004.

P. E. Wright and H. J. Dyson, Intrinsically unstructured proteins: Re-assessing the protein structurefunction paradigm, J. Mol. Biol, vol.293, issue.2, pp.321-331, 1999.

P. E. Wright and H. J. Dyson, Linking folding and binding, Curr. Opin. Struct. Biol, vol.19, issue.1, pp.31-38, 2009.

G. Wulf, P. Garg, Y. Liou, D. Iglehart, and K. P. Lu, Modeling breast cancer in vivo and ex vivo reveals an essential role of Pin1 in tumorigenesis, EMBO J, vol.23, issue.16, pp.3397-3407, 2004.

M. Wyszynski, J. Lin, A. Rao, E. Nigh, A. H. Beggs et al., Competitive binding of ?-actinin and calmodulin to the NMDA receptor, Nature, vol.385, issue.6615, pp.439-442, 1997.

Y. Xie, A. M. Pendergast, and M. C. Hung, Dominant-negative mutants of Grb2 induced reversal of the transformed phenotypes caused by the point mutation-activated rat HER-2/Neu, J. Biol. Chem, vol.270, issue.51, pp.30717-30741, 1995.

T. Yamazaki, K. Zaal, D. Hailey, J. Presley, J. Lippincott-schwartz et al., Role of Grb2 in EGF-stimulated EGFR internalization, J. Cell Sci, vol.115, pp.1791-802, 2002.

Y. Yarden and G. Pines, The ERBB network: at last, cancer therapy meets systems biology, Nat. Rev. Cancer, vol.12, issue.8, pp.553-563, 2012.

Y. Yarden and J. Schlessinger, Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation, Biochemistry, vol.26, issue.5, pp.1434-1442, 1987.

Y. Yarden and M. X. Sliwkowski, Untangling the ErbB signalling network, Nat. Rev. Mol. Cell Biol, vol.2, issue.2, pp.127-137, 2001.

S. Yuzawa, M. Yokochi, H. Hatanaka, K. Ogura, M. Kataoka et al., Solution structure of Grb2 reveals extensive flexibility necessary for target recognition, J. Mol. Biol, vol.306, issue.3, pp.527-564, 2001.

K. Zaoui, S. Honoré, D. Isnardon, D. Braguer, and A. Badache, Memo-RhoA-mDia1 signaling controls microtubules, the actin network, and adhesion site formation in migrating cells, J. Cell Biol, vol.183, issue.3, pp.401-408, 2008.

O. Zhang and J. D. Forman-kay, Structural Characterization of Folded and Unfolded States of an SH3 Domain in Equilibrium in Aqueous Buffer, Biochemistry, vol.34, issue.20, pp.6784-6794, 1995.

X. Zhang, J. Gureasko, K. Shen, P. A. Cole, and J. Kuriyan, An Allosteric Mechanism for Activation of the Kinase Domain of Epidermal Growth Factor Receptor, Cell, vol.125, issue.6, pp.1137-1149, 2006.

Y. Zhang, J. L. Ptacin, E. C. Fischer, H. R. Aerni, C. E. Caffaro et al., A semi-synthetic organism that stores and retrieves increased genetic information, Nature, vol.551, issue.7682, pp.644-647, 2017.

H. X. Zhou, Intrinsic disorder: Signaling via highly specific but short-lived association, Trends Biochem. Sci, vol.37, issue.2, pp.43-48, 2012.

H. X. Zhou, X. Pang, and C. Lu, Rate constants and mechanisms of intrinsically disordered proteins binding to structured targets, Phys. Chem. Chem. Phys, vol.14, issue.30, pp.10466-10476, 2012.

M. M. Zhou, K. S. Ravichandran, E. F. Olejniczak, A. M. Petros, R. P. Meadows et al., Structure and ligand recognition of the phosphotyrosine binding domain of Shc, Nature, vol.378, issue.6557, pp.584-92, 1995.

G. Zhu, Y. Liu, and S. Shaw, Protein Kinase Specificity: A Strategic Collaboration between Kinase Peptide Specificity and Substrate Recruitment, Cell Cycle, vol.4, issue.1, pp.52-56, 2005.