Structural Conservation Predominates Over Sequence Variability in the Crown of HIV Type 1's V3 Loop
Structural Conservation Predominates Over Sequence Variability in the Crown of HIV Type 1's V3 Loop
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DOI：
10.1089/aid.2009.0254
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发表时间：
2010-06-01
影响因子：
1.5
通讯作者：
Cardozo, Timothy
中科院分区：
文献类型：
--
作者：
Almond, David;Kimura, Tetsuya;Cardozo, Timothy
HIV-1 的多样性对于疫苗设计来说是一个令人困惑的问题，因为人类免疫反应似乎倾向于对任何给定的 HIV-1 病毒株产生不良反应或毒株特异性反应。这种多样性的一个重要部分表现为 HIV-1 表面包膜糖蛋白环中的序列变异。在这里，我们显示第三个变量 (V3) 环冠中最可变的序列位置聚集在 V3 环 β-发夹构象的一个面表面上的一个小区域。这些结果提供了 gp120 V3 环的新颖可视化，特别证明了高度序列可变区域中保守的三维结构的惊人优势。从结构的角度来看，HIV-1“主要中和结构域”的这个区域的多样性似乎比以前认识的要少。
The diversity of HIV-1 is a confounding problem for vaccine design, as the human immune response appears to favor poor or strain-specific responses to any given HIV-1 virus strain. A significant portion of this diversity is manifested as sequence variability in the loops of HIV-1's surface envelope glycoprotein. Here we show that the most variable sequence positions in the third variable (V3) loop crown cluster to a small zone on the surface of one face of the V3 loop beta-hairpin conformation. These results provide a novel visualization of the gp120 V3 loop, specifically demonstrating a surprising preponderance of conserved three-dimensional structure in a highly sequence-variable region. From a structural point of view, there appears to be less diversity in this region of the HIV-1 "principle neutralizing domain" than previously appreciated.