title: Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120.
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.
authors: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Anthony P
authors: AP
authors: West
authors: Ron
authors: R
authors: Diskin
authors: Michel C
authors: MC
authors: Nussenzweig
authors: Pamela J
authors: PJ
authors: Bjorkman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D005854:Germ Cells / Q000276:immunology; D015483:HIV Antibodies / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D008969:Molecular Sequence Data; D016296:Mutagenesis; D059645:Mutation Rate; D009500:Neutralization Tests; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D020349:Surface Plasmon Resonance
chemical_list: D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120