Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

被引:125
作者
Mao, Youdong [1 ]
Wang, Liping [1 ]
Gu, Christopher [1 ]
Herschhorn, Alon [1 ]
Xiang, Shi-Hua [1 ]
Haim, Hillel [1 ]
Yang, Xinzhen [2 ]
Sodroski, Joseph [1 ,3 ,4 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Immunobiol,Dept Canc Immunol & A, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA
[4] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZATION EPITOPE; CONFORMATIONAL-CHANGES; VARIABLE LOOPS; AIDS PATIENTS; CD4; BINDING; GP120; CORE; HTLV-III; GP41; ANTIBODY;
D O I
10.1038/nsmb.2351
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 trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric glycoprotein precursor, gp160, into three gp120 and three gp41 subunits. Here, we describe an similar to 11-angstrom cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain and a trimer-association domain of gp120 composed of the V1, V2 and V3 variable regions. The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host.
引用
收藏
页码:893 / 899
页数:7
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