Disulfide exchange in domain 2 of CD4 is required for entry of HIV-I
Disulfide exchange in domain 2 of CD4 is required for entry of HIV-I
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DOI：
10.1038/ni815
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发表时间：
2002-08-01
影响因子：
30.5
通讯作者：
Hogg, PJ
中科院分区：
文献类型：
--
作者：
Matthias, LJ;Yam, PTW;Hogg, PJ
CD 4是免疫球蛋白受体超家族的成员，在免疫系统中介导细胞-细胞相互作用，是HIV-1的主要受体。CD 4的细胞外部分是四个免疫球蛋白样结构域D1至D4的串联。D1、D2和D4结构域各自含有二硫键。我们在这里表明，D2二硫键是氧化还原活性。硫醇的氧化还原状态（二硫化物与二硫醇）似乎受到硫氧还蛋白的调节，硫氧还蛋白由CD 4（+）T细胞分泌。用亲水性三价砷将CD 4和硫氧还蛋白活性位点二硫醇锁定在还原状态，阻断了HIV-1进入易感细胞。这些发现表明，CD 4 D2的氧化还原变化对HIV-1进入很重要，并代表了HIV-1进入抑制剂的新靶点。
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.