Structural basis for membrane anchoring of HIV-1 envelope spike

被引：148

作者：

Dev, Jyoti ^{[1
,2
]}

Park, Donghyun ^{[3
]}

Fu, Qingshan ^{[1
]}

Chen, Jia ^{[3
,4
]}

Ha, Heather Jiwon ^{[3
]}

Ghantous, Fadi ^{[5
]}

Herrmann, Tobias

Chang, Weiting ^{[2
,3
]}

Liu, Zhijun ^{[6
]}

Frey, Gary ^{[3
,4
]}

Seaman, Michael S. ^{[5
]}

Chen, Bing ^{[3
,4
]}

Chou, James J. ^{[1
,6
]}

机构：

[1] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA

[2] Harvard Med Sch, Virol Program, 250 Longwood Ave, Boston, MA 02115 USA

[3] Boston Childrens Hosp, Div Mol Med, 3 Blackfan St, Boston, MA 02115 USA

[4] Harvard Med Sch, Dept Pediat, 300 Longwood Ave, Boston, MA 02115 USA

[5] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, 330 Brookline Ave, Boston, MA 02215 USA

[6] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, State Key Lab Mol Biol, Shanghai 200031, Peoples R China

来源：

SCIENCE | 2016年 / 353卷 / 6295期

关键词：

SPANNING DOMAIN; GLYCOPROTEIN; FUSION; NEUTRALIZATION; RECOGNITION; EXPRESSION; MUTATIONS; MECHANISM; REGION; TRIMER;

D O I：

10.1126/science.aaf7066

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 envelope spike (Env) is a type I membrane protein that mediates viral entry. We used nuclear magnetic resonance to determine an atomic structure of the transmembrane (TM) domain of HIV-1 Env reconstituted in bicelles that mimic a lipid bilayer. The TM forms a well-ordered trimer that protects a conserved membrane-embedded arginine. An aminoterminal coiled-coil and a carboxyl-terminal hydrophilic core stabilize the trimer. Individual mutations of conserved residues did not disrupt the TM trimer and minimally affected membrane fusion and infectivity. Major changes in the hydrophilic core, however, altered the antibody sensitivity of Env. These results show how a TM domain anchors, stabilizes, and modulates a viral envelope spike and suggest that its influence on Env conformation is an important consideration for HIV-1 immunogen design.

引用

页码：172 / 175

页数：4

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