Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120
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 s...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 30; pp. E2083 - E2090 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
24.07.2012
National Acad Sciences |
Series | PNAS Plus |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | http://dx.doi.org/10.1073/pnas.1208984109 Contributed by Pamela J. Bjorkman, May 30, 2012 (sent for review May 2, 2012) Author contributions: A.P.W. designed and performed research; A.P.W., R.D., and P.J.B. analyzed data; and A.P.W., M.C.N., and P.J.B. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1208984109 |