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Caractérisation de l'interaction entre la glycoprotéine d'enveloppe gp120 du VIH-1 et les héparanes sulfate : importance des changements conformationnels induits par la liaison à CD4

Abstract : During viral entry, HIV surface glycoprotein gp120 binds to CD4, thereby anchoring the virus to the host cell surface. This interaction induces conformational changes within gp120 that expose CD4-induced (CD4i) epitope, the binding site for coreceptors (usually a member of the chemokine receptor family). In addition, HIV binds to heparan sulphate (HS), an abundant cell surface polysaccharide, through several domains of gp120, including CD4i. Thus, it may be possible to inhibit HIV binding to cells, using soluble molecules derived from HS. In this context, we proposed to characterise further the structural features of the CD4i/HS interaction. First, we produced and purified gp120 proteins mutated on four residues within CD4i, suspected to interact with HS and, then, we studied their ability to bind to heparin by SPR. A second aspect of the project concerned the development of a new strategy for defining critical residues involved in protein/heparin interactions. Results led to the identification of four heparin binding domains within gp120 and, in particular, three residues within CD4i (R419, K421 and K432) were reported to bind heparin. These studies should contribute to clarify the role of HS in the mechanism of HIV binding to the cell surface and provide precise structural information enabling the definition of HS-derived inhibitors of viral entry.
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https://tel.archives-ouvertes.fr/tel-00260979
Contributor : Elodie Crublet <>
Submitted on : Wednesday, March 5, 2008 - 11:17:32 PM
Last modification on : Tuesday, October 6, 2020 - 4:12:03 PM
Long-term archiving on: : Thursday, May 20, 2010 - 7:48:03 PM

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  • HAL Id : tel-00260979, version 1

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Elodie Crublet. Caractérisation de l'interaction entre la glycoprotéine d'enveloppe gp120 du VIH-1 et les héparanes sulfate : importance des changements conformationnels induits par la liaison à CD4. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2008. Français. ⟨tel-00260979⟩

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