|Title||Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||West AP, Diskin R, Nussenzweig MC, Bjorkman PJ|
|Journal||Proc Natl Acad Sci U S A|
|Date Published||2012 Jul 24|
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.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|