Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer

被引：573

作者：

Lyumkis, Dmitry ^{[1
,2
]}

Julien, Jean-Philippe ^{[2
,3
,4
]}

de Val, Natalia ^{[2
,3
]}

Cupo, Albert ^{[5
]}

Potter, Clinton S. ^{[1
,2
]}

Klasse, Per-Johan ^{[5
]}

Burton, Dennis R. ^{[3
,6
,7
,8
]}

Sanders, Rogier W. ^{[5
,9
]}

Moore, John P. ^{[5
]}

Carragher, Bridget ^{[1
,2
]}

Wilson, Ian A. ^{[2
,3
,4
,6
]}

Ward, Andrew B. ^{[2
,3
,6
]}

机构：

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

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

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

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

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

[6] Scripps Res Inst, Neutralizing Antibody Ctr, Int AIDS Vaccine Initiat IAVI, La Jolla, CA 92037 USA

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

[8] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA

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

来源：

SCIENCE | 2013年 / 342卷 / 6165期

基金：

加拿大健康研究院; 欧洲研究理事会;

关键词：

NEUTRALIZING ANTIBODIES; MOLECULAR ARCHITECTURE; GLYCOPROTEIN COMPLEX; CRYSTAL-STRUCTURE; GP120; VIRUS; RESOLUTION; RECOGNITION; DISPLAY; BINDING;

D O I：

10.1126/science.1245627

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 HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described.

引用

页码：1484 / 1490

页数：7

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