Structural Basis for the Antiviral Activity of BST-2/Tetherin and Its Viral Antagonism.
Structural Basis for the Antiviral Activity of BST-2/Tetherin and Its Viral Antagonism.
复制标题
BST-2/Tetherin及其病毒拮抗作用的抗病毒活性的结构基础。
DOI：
10.3389/fmicb.2011.00250
复制
发表时间：
2011
影响因子：
5.2
通讯作者：
Tokunaga K
中科院分区：
文献类型：
--
作者：
Arias JF;Iwabu Y;Tokunaga K
干扰素诱导宿主限制因子骨髓基质抗原2 （BST-2/tetherin）阻断HIV-1和其他包膜病毒的释放。反过来，这些病毒进化出了特异性拮抗剂来对抗这种宿主抗病毒分子，如HIV-1蛋白Vpu。BST-2是一种II型跨膜蛋白，具有不同寻常的拓扑结构，包括一个n端细胞质尾部（CT），随后是一个跨膜（TM）结构域，一个卷曲卷曲的细胞外（EC）结构域，以及一个位于C端的糖基磷脂酰肌醇（GPI）锚定。我们和其他人发现BST-2通过用两个相反的膜锚连接宿主和病毒粒子膜来限制包膜病毒的释放，删除任何一个都完全取消抗病毒活性。EC结构域也显示出抗病毒功能所需的保守结构特性。它含有几个不稳定的氨基酸，使分子具有构象灵活性，以维持蛋白质作为病毒粒子系链的功能，以及三个保守的半胱氨酸残基，介导BST-2的同型二聚化，以及作为分离膜锚的分子标尺。相反，病毒粒子的有效释放是由HIV-1 Vpu蛋白和其他病毒拮抗剂促进的。我们的团队和其他人从突变分析中提供的证据表明，Vpu对bst -2介导的病毒限制的拮抗需要它们相互的TM结构域的高度特异性相互作用。最新的结构建模研究结果进一步支持和扩展了这一解释，表明这些TM结构域的保守螺旋面上的关键氨基酸是Vpu-BST-2相互作用和拮抗所必需的。本文就BST-2抗病毒功能的结构基础以及BST-2特异性病毒拮抗作用的研究进展进行综述。
The interferon-inducible host restriction factor bone marrow stromal antigen 2 (BST-2/tetherin) blocks the release of HIV-1 and other enveloped viruses. In turn, these viruses have evolved specific antagonists to counteract this host antiviral molecule, such as the HIV-1 protein Vpu. BST-2 is a type II transmembrane protein with an unusual topology consisting of an N-terminal cytoplasmic tail (CT) followed by a single transmembrane (TM) domain, a coiled-coil extracellular (EC) domain, and a glycosylphosphatidylinositol (GPI) anchor at the C terminus. We and others showed that BST-2 restricts enveloped virus release by bridging the host and virion membranes with its two opposing membrane anchors and that deletion of either one completely abrogates antiviral activity. The EC domain also shows conserved structural properties that are required for antiviral function. It contains several destabilizing amino acids that confer the molecule with conformational flexibility to sustain the protein’s function as a virion tether, and three conserved cysteine residues that mediate homodimerization of BST-2, as well as acting as a molecular ruler that separates the membrane anchors. Conversely, the efficient release of virions is promoted by the HIV-1 Vpu protein and other viral antagonists. Our group and others provided evidence from mutational analyses indicating that Vpu antagonism of BST-2-mediated viral restriction requires a highly specific interaction of their mutual TM domains. This interpretation is further supported and expanded by the findings of the latest structural modeling studies showing that critical amino acids in a conserved helical face of these TM domains are required for Vpu–BST-2 interaction and antagonism. In this review, we summarize the current advances in our understanding of the structural basis for BST-2 antiviral function as well as BST-2-specific viral antagonism.
登录
查看更多内容
影响因子：
6.7
作者：
Casartelli N;Sourisseau M;Feldmann J;Guivel-Benhassine F;Mallet A;Marcelin AG;Guatelli J;Schwartz O
通讯作者：
Schwartz O
影响因子：
30.3
作者：
Hinz A;Miguet N;Natrajan G;Usami Y;Yamanaka H;Renesto P;Hartlieb B;McCarthy AA;Simorre JP;Göttlinger H;Weissenhorn W
通讯作者：
Weissenhorn W
影响因子：
64.8
作者：
COHEN, EA;TERWILLIGER, EF;HASELTINE, WA
通讯作者：
HASELTINE, WA
DOI：
10.1073/pnas.0907075106
发表时间：
2009-12-08
影响因子：
11.1
作者：
Gupta, Ravindra K.;Mlcochova, Petra;Towers, Greg J.
通讯作者：
Towers, Greg J.
影响因子：
30.3
作者：
Goffinet, Christine;Allespach, Ina;Keppler, Oliver T.
通讯作者：
Keppler, Oliver T.