Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

被引:10
作者
Bellamy-McIntyre, Anna K. [1 ,2 ]
Baer, Severine [3 ,4 ]
Ludlow, Louise [1 ]
Drummer, Heidi E. [1 ,2 ,5 ]
Poumbourios, Pantelis [1 ,2 ]
机构
[1] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3004, Australia
[2] Monash Univ, Dept Microbiol, Melbourne, Vic 3168, Australia
[3] Deutsch Krebsforschungszentrum, Program Infect & Canc, Abt F010, Heidelberg, Germany
[4] Deutsch Krebsforschungszentrum, INSERM, U701, Heidelberg, Germany
[5] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
HIV-1; Receptor; gp41; Disulfide-bonded region; Membrane fusion; TRANSMEMBRANE GLYCOPROTEIN; ENVELOPE GLYCOPROTEIN; ATOMIC-STRUCTURE; HIV-1; GP120; ECTODOMAIN; ISOMERIZATION; ARCHITECTURE; ASSOCIATION; STABILITY; ANTIBODY;
D O I
10.1016/j.bbrc.2010.03.071
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1(QH1549.13) blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:904 / 908
页数:5
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