Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D

被引：176
作者：
Stanfield, RL
Gorny, MK
Williams, C
Zolla-Pazner, S
Wilson, IA
机构：
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] NYU, Sch Med, New York, NY 10010 USA
[4] Vet Adm Med Ctr, New York, NY 10010 USA
来源：
STRUCTURE | 2004年 / 12卷 / 02期
关键词：
D O I：
10.1016/j.str.2004.01.003
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 Angstrom resolution reveals that the peptide beta hairpin forms a three-stranded mixed beta 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.
引用
收藏
页码：193 / 204
页数：12
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