Structural Rationale for the Broad Neutralization of HIV-1 by Human Monoclonal Antibody 447-52D

Robyn L. Stanfield, Miroslaw K. Gorny, Constance Williams, Susan Zolla-Pazner, Ian A. Wilson

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

Abstract

447-52D is a human monoclonal antibody isolated from a heterohybridoma derived from an HIV-1-infected individual. This antibody recognizes the hypervariable gp120 V3 loop, and neutralizes both X4 and R5 primary isolates, making it one of the most effective anti-V3 antibodies characterized to date. The crystal structure of the 447-52D Fab in complex with a 16-mer V3 peptide at 2.5 Å resolution reveals that the peptide β hairpin forms a three-stranded mixed β sheet with complementarity determining region (CDR) H3, with most of the V3 side chains exposed to solvent. Sequence specificity is conferred through interaction of the type-II turn (residues GPGR) at the apex of the V3 hairpin with the base of CDR H3. This novel mode of peptide-antibody recognition enables the antibody to bind to many different V3 sequences where only the GPxR core epitope is absolutely required.

Original languageEnglish
Pages (from-to)193-204
Number of pages12
JournalStructure
Volume12
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

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