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Conserved Structural Elements in the V3 Crown of HIV-1 gp120

Journal Article · · Nature Structural and Molecular Biology
DOI:https://doi.org/10.1038/nsmb.1861· OSTI ID:1019888

Binding of the third variable region (V3) of the HIV-1 envelope glycoprotein gp120 to the cell-surface coreceptors CCR5 or CXCR4 during viral entry suggests that there are conserved structural elements in this sequence-variable region. These conserved elements could serve as epitopes to be targeted by a vaccine against HIV-1. Here we perform a systematic structural analysis of representative human anti-V3 monoclonal antibodies in complex with V3 peptides, revealing that the crown of V3 has four conserved structural elements: an arch, a band, a hydrophobic core and the peptide backbone. These are either unaffected by or are subject to minimal sequence variation. As these regions are targeted by cross-clade neutralizing human antibodies, they provide a blueprint for the design of vaccine immunogens that could elicit broadly cross-reactive protective antibodies.

Research Organization:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Organization:
DOE - OFFICE OF SCIENCE
DOE Contract Number:
AC02-98CH10886
OSTI ID:
1019888
Report Number(s):
BNL--95734-2011-JA
Journal Information:
Nature Structural and Molecular Biology, Journal Name: Nature Structural and Molecular Biology Journal Issue: 8 Vol. 17; ISSN 1545-9993
Country of Publication:
United States
Language:
English