Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120

被引：245

作者：

Chen, Lei ^{[1
]}

Kwon, Young Do ^{[1
]}

Zhou, Tongqing ^{[1
]}

Wu, Xueling ^{[1
]}

O'Dell, Sijy ^{[1
]}

Cavacini, Lisa ^{[2
]}

Hessell, Ann J. ^{[3
,4
,5
]}

Pancera, Marie ^{[1
]}

Tang, Min ^{[1
]}

Xu, Ling ^{[1
]}

Yang, Zhi-Yong ^{[1
]}

Zhang, Mei-Yun ^{[6
]}

Arthos, James ^{[7
]}

Burton, Dennis R. ^{[3
,4
,5
,8
,9
]}

Dimitrov, Dimiter S. ^{[6
]}

Nabel, Gary J. ^{[1
]}

Posner, Marshall R. ^{[2
]}

Sodroski, Joseph ^{[10
]}

Wyatt, Richard ^{[1
]}

Mascola, John R. ^{[1
]}

Kwong, Peter D. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA

[3] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA

[4] Scripps Res Inst, Dept Microbial Sci, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA

[6] NCI, Ctr Canc Res, Frederick, MD 21702 USA

[7] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[8] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA

[9] Harvard Univ, Boston, MA 02114 USA

[10] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

来源：

SCIENCE | 2009年 / 326卷 / 5956期

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODIES; BINDING-SITE; EFFICIENT NEUTRALIZATION; ENVELOPE GLYCOPROTEINS; INFECTED INDIVIDUALS; PROTEIN; PANEL; CRYSTALLIZATION;

D O I：

10.1126/science.1175868

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.

引用

页码：1123 / 1127

页数：5

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