Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120.

TitleStructural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120.
Publication TypeJournal Article
Year of Publication2012
AuthorsWest AP, Diskin R, Nussenzweig MC, Bjorkman PJ
JournalProc Natl Acad Sci U S A
Volume109
Issue30
PaginationE2083-90
Date Published2012 Jul 24
ISSN1091-6490
Abstract

A large number of anti-HIV-1 antibodies targeting the CD4-binding site (CD4bs) on the envelope glycoprotein gp120 have recently been reported. These antibodies, typified by VRC01, are remarkable for both their breadth and their potency. Crystal structures have revealed a common mode of binding for several of these antibodies; however, the precise relationship among CD4bs antibodies remains to be defined. Here we analyze existing structural and sequence data, propose a set of signature features for potent VRC01-like (PVL) antibodies, and verify the importance of these features by mutagenesis. The signature features explain why PVL antibodies derive from a single germ-line human V(H) gene segment and why certain gp120 sequences are associated with antibody resistance. Our results bear on vaccine development and structure-based design to improve the potency and breadth of anti-CD4bs antibodies.

DOI10.1073/pnas.1208984109
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22745174