Disulfide exchange in domain 2 of CD4 is required for entry of HIV-I

被引:158
作者
Matthias, LJ
Yam, PTW
Jiang, XM
Vandegraaff, N
Li, P
Poumbourios, P
Donoghue, N
Hogg, PJ [1 ]
机构
[1] Univ New S Wales, Sch Med Sci, Ctr Thrombosis & Vasc Res, Sydney, NSW 2052, Australia
[2] Prince Wales Hosp, Dept Haematol, Sydney, NSW 2052, Australia
[3] Inst Med & Vet Sci, Infect Dis Labs, Natl Ctr HIV Virol Res, Adelaide, SA 5000, Australia
[4] St Vincents Inst Med Res, Virol Unit, Fitzroy, Vic 3065, Australia
关键词
D O I
10.1038/ni815
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD4, a member of the immunoglobulin superfamily of receptors that mediates cell-cell interactions in the immune system, is the primary receptor for HIV-1. The extracellular portion of CD4 is a concatenation of four immunoglobulin-like domains, D1 to D4. The D1, D2 and D4 domains each contain a disulfide bond. We show here that the D2 disulfide bond is redox-active. The redox state of the thiols (disulfide versus dithiol) appeared to be regulated by thioredoxin, which is secreted by CD4(+) T cells. Locking the CD4 and the thioredoxin active-site dithiols in the reduced state with a hydrophilic trivalent arsenical blocked entry of HIV-1 into susceptible cells. These findings indicate that redox changes in CD4 D2 are important for HIV-1 entry and represent a new target for HIV-1 entry inhibitors.
引用
收藏
页码:727 / 732
页数:6
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