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Cell surface assembly of HIV gp41 six-helix bundles for facile, quantitative measurements of hetero-oligomeric interactions.

ABSTRACT: Helix-helix interactions are fundamental to many biological signals and systems and are found in homo- or heteromultimerization of signaling molecules as well as in the process of virus entry into the host. In HIV, virus-host membrane fusion during infection is mediated by the formation of six-helix bundles (6HBs) from homotrimers of gp41, from which a number of synthetic peptides have been derived as antagonists of virus entry. Using a yeast surface two-hybrid (YS2H) system, a platform designed to detect protein-protein interactions occurring through a secretory pathway, we reconstituted 6HB complexes on the yeast surface, quantitatively measured the equilibrium and kinetic constants of soluble 6HB, and delineated the residues influencing homo-oligomeric and hetero-oligomeric coiled-coil interactions. Hence, we present YS2H as a platform for the facile characterization and design of antagonistic peptides for inhibition of HIV and many other enveloped viruses relying on membrane fusion for infection, as well as cellular signaling events triggered by hetero-oligomeric coiled coils.

SUBMITTER: Hu X

PROVIDER: S-EPMC3731752 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Cell surface assembly of HIV gp41 six-helix bundles for facile, quantitative measurements of hetero-oligomeric interactions.

Hu Xuebo X Saha Piyali P Chen Xiaoyue X Kim Dogeun D Devarasetty Mahesh M Varadarajan Raghavan R Jin Moonsoo M MM

Journal of the American Chemical Society 20120828 36

Helix-helix interactions are fundamental to many biological signals and systems and are found in homo- or heteromultimerization of signaling molecules as well as in the process of virus entry into the host. In HIV, virus-host membrane fusion during infection is mediated by the formation of six-helix bundles (6HBs) from homotrimers of gp41, from which a number of synthetic peptides have been derived as antagonists of virus entry. Using a yeast surface two-hybrid (YS2H) system, a platform designed ...[more]

PMID: 22888993

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Dataset Information

Cell surface assembly of HIV gp41 six-helix bundles for facile, quantitative measurements of hetero-oligomeric interactions.

Publications

Cell surface assembly of HIV gp41 six-helix bundles for facile, quantitative measurements of hetero-oligomeric interactions.

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