Structural Analysis of Human and Macaque mAbs 2909 and 2.5B: Implications for the Configuration of the Quaternary Neutralizing Epitope of HIV-1 gp120

被引：19

作者：

Spurrier, Brett ^{[1
]}

Sampson, Jared M. ^{[1
]}

Totrov, Maxim ^{[2
]}

Li, Huiguang ^{[1
]}

O'Neal, Timothy ^{[3
]}

Williams, Constance ^{[3
]}

Robinson, James ^{[4
]}

Gorny, Miroslaw K. ^{[3
]}

Zolla-Pazner, Susan ^{[3
,5
]}

Kong, Xiang-Peng ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA

[2] Molsoft LLC, La Jolla, CA 92037 USA

[3] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[4] Tulane Univ, Dept Pediat, Med Ctr, New Orleans, LA 70012 USA

[5] Vet Affairs New York Harbor Healthcare Syst, New York, NY 10010 USA

来源：

STRUCTURE | 2011年 / 19卷 / 05期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; BINDING MODE; SOLUBLE CD4; PROTEIN; IDENTIFICATION; DOCKING; COMPLEX; REVEAL;

D O I：

10.1016/j.str.2011.02.012

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：

The quaternary neutralizing epitope (ONE) of HIV-1 gp120 is preferentially expressed on the trimeric envelope spikes of intact HIV virions, and ONE-specific monoclonal antibodies (mAbs) potently neutralize HIV-1. Here, we present the crystal structures of the Fabs of human mAb 2909 and macaque mAb 2.5B. Both. mAbs have long beta hairpin CDR H3 regions >20 angstrom in length that are each situated at the center of their respective antigen-binding sites. Computational analysis showed that the paratopes include the whole CDR H3, while additional CDR residues form shallow binding pockets. Structural modeling suggests a way to understand the configuration of QNEs and the antigen-antibody interaction for ONE mAbs. Our data will be useful in designing immunogens that may elicit potent neutralizing QNE Abs.

引用

页码：691 / 699

页数：9

共 41 条

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