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Etude structurale des petites protéines G : Rap2A dans un complexe non catalytique avec le GTP et Arf6 en complexe avec du GDP

Abstract : Small G proteins are able to bind GDP or GTP in different conformations. The conformational changes between GDP-form and GTP-form allow small G proteins to bind different cellular partners and to play the role of a molecular swicth in the cell. The GDP/GTP cycle of small G proteins doesn't work without Guanine nucleotide Exchange Factors (GEF) which exchange GDP for GTP and Guanine Activating Proteins (GAP) which hydrolyze GTP to GDP. Small G proteins are regulator of important cellular functions as cellular differentiation and growth, cytoskeleton dynamic and organization, and intracellular transports. Many small G protein structures are now resolved and allow to define general folding and conformational changes of these proteins. As a first project, we have resolved the structure of Rap2A, an oncogene Ras homologue in a non-catalytic complex with its natural ligand the GTP. This study shows a new interaction in nucleotide binding site between tyrosine 32 and the gamma phosphate of GTP. Moreover, we discuss the definition of flexible regions and their hinges for this structure and in the light of expanding database of small G protein structures. In other project, we have resolved the structure of Arf6 in complex with GDP. This study provide a structural basis to understand how Arf6 and Arf1, which share high sequence homology could be distinguished by their Guanine nucleotide Exchange Factor. Moreover, we have observed that one sequence difference between Arf1 (Ile42) and Arf6 (Ser38) outside the nucleotide binding site affects its configuration and the nucleotide binding properties. To conclude, we discuss the structural basis that could explain how small G proteins which share high sequence homology could be distinguished by partners.
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https://tel.archives-ouvertes.fr/tel-00004186
Contributor : Julie Menetrey <>
Submitted on : Thursday, January 15, 2004 - 6:42:36 PM
Last modification on : Thursday, December 10, 2020 - 10:52:46 AM
Long-term archiving on: : Wednesday, September 12, 2012 - 12:25:24 PM

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  • HAL Id : tel-00004186, version 1

Citation

Julie Menetrey. Etude structurale des petites protéines G : Rap2A dans un complexe non catalytique avec le GTP et Arf6 en complexe avec du GDP. Biochimie [q-bio.BM]. Université Pierre et Marie Curie - Paris VI, 2000. Français. ⟨tel-00004186⟩

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