Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer

被引：690

作者：

Julien, Jean-Philippe ^{[1
,2
,3
]}

Cupo, Albert ^{[4
]}

Sok, Devin ^{[2
,3
,5
]}

Stanfield, Robyn L. ^{[1
,2
,3
]}

Lyumkis, Dmitry ^{[1
,6
]}

Deller, Marc C. ^{[7
]}

Klasse, Per-Johan ^{[4
]}

Burton, Dennis R. ^{[2
,3
,5
,8
]}

Sanders, Rogier W. ^{[4
,9
]}

Moore, John P. ^{[4
]}

Ward, Andrew B. ^{[1
,2
,3
]}

Wilson, Ian A. ^{[1
,2
,3
,7
,10
]}

机构：

[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

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

[3] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[4] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[5] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[6] Scripps Res Inst, Natl Resource Automated Mol Microscopy, La Jolla, CA 92037 USA

[7] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA

[8] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02129 USA

[9] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[10] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

SCIENCE | 2013年 / 342卷 / 6165期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会; 欧洲研究理事会;

关键词：

N-GLYCAN RECOGNITION; MOLECULAR ARCHITECTURE; POTENT NEUTRALIZATION; GLYCOPROTEIN COMPLEX; V3; LOOP; GP120; VIRUS; ANTIBODY; BROAD; REGION;

D O I：

10.1126/science.1245625

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：

HIV-1 entry into CD4(+) target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP. 664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design.

引用

页码：1477 / 1483

页数：7

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