Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4
Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4
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DOI：
10.1126/science.1145373
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发表时间：
2007-09-28
期刊：
影响因子：
56.9
通讯作者：
Kwong, Peter D.
中科院分区：
文献类型：
--
作者：
Huang, Chih-chin;Lam, Son N.;Kwong, Peter D.
CCR5 辅助受体与 HIV-1 gp120 包膜糖蛋白结合，促进 HIV-1 进入细胞。它的 N 末端是酪氨酸硫酸化的，许多与 gp120 上的辅助受体结合位点反应的抗体也是如此。我们应用核磁共振和晶体学技术分析了 CCR5 N 末端的结构以及与 gp120 和 CD4 复合的酪氨酸硫酸化抗体 412d 的结构。 CCR5（α 螺旋）和 412d（延伸环）的酪氨酸硫酸化区域的构象惊人地不同。尽管如此，CCR5 和 412d 上的关键磺基酪氨酸在 gp120 中诱导类似的结构重排。这些结果现在为理解病毒进入过程中 HIV-1 与 CCR5 N 末端的相互作用提供了一个框架，并定义了 gp120 上的一个保守位点，其对磺基酪氨酸的识别引起免疫系统的翻译后拟态。
The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended-loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.