National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
HIVRAD P01 P01AI10014 (P.J.B.)
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P50 8 P50 AI150464-13 (P.J.B.)
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2019 タイトル: Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody. 著者: Zhi Yang / Haoqing Wang / Albert Z Liu / Harry B Gristick / Pamela J Bjorkman / 要旨: The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120-gp41) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor ...The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120-gp41) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5's tyrosine-sulfated amino (N) terminus, release of the gp41 fusion peptide and fusion. We present 3.3 Å and 3.5 Å cryo-EM structures of E51, a tyrosine-sulfated coreceptor-mimicking antibody, complexed with a CD4-bound open HIV-1 native-like Env trimer. Two classes of asymmetric Env interact with E51, revealing tyrosine-sulfated interactions with gp120 mimicking CCR5 interactions, and two conformations of gp120-gp41 protomers (A and B protomers in AAB and ABB trimers) that differ in their degree of CD4-induced trimer opening and induction of changes to the fusion peptide. By integrating the new structural information with previous closed and open envelope trimer structures, we modeled the order of conformational changes on the path to coreceptor binding site exposure and subsequent viral-host cell membrane fusion.
全体 : Cryo-EM map for class-1 asymmetric open conformation of HIV-1 Env...
全体
名称: Cryo-EM map for class-1 asymmetric open conformation of HIV-1 Env trimer BG505 SOSIP in complex with sCD4 and E51 Fab
要素
複合体: Cryo-EM map for class-1 asymmetric open conformation of HIV-1 Env trimer BG505 SOSIP in complex with sCD4 and E51 Fab
複合体: Envelope glycoprotein gp120
タンパク質・ペプチド: Envelope glycoprotein gp120
複合体: T-cell surface glycoprotein CD4
タンパク質・ペプチド: T-cell surface glycoprotein CD4
複合体: E51 Fab
タンパク質・ペプチド: E51 Fab heavy chain
タンパク質・ペプチド: E51 Fab light chain
複合体: Envelope glycoprotein gp41
タンパク質・ペプチド: Envelope glycoprotein gp41
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
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超分子 #1: Cryo-EM map for class-1 asymmetric open conformation of HIV-1 Env...
超分子
名称: Cryo-EM map for class-1 asymmetric open conformation of HIV-1 Env trimer BG505 SOSIP in complex with sCD4 and E51 Fab タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5