Structural basis for germline 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 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 VH 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.

• Publication year

  2012

• Venue

  Retrovirology

• Publication date

  2012-06-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1742-4690-9-S2-O33PMID 22745174PMCID 3441645
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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