Caging the Beast: TRIM5α Binding to the HIV-1 Core
Caging the Beast: TRIM5α Binding to the HIV-1 Core
复制标题
DOI：
10.3390/v3050423
复制
发表时间：
2011-05-01
期刊：
影响因子：
4.7
通讯作者：
Diaz-Griffero, Felipe
中科院分区：
文献类型：
--
作者：
Diaz-Griffero, Felipe
有效的HIV-1抑制剂TRIM 5 alpha通过加速HIV-1的脱壳来阻断HIV-1感染。已知TRIM 5 α形成高阶自缔合复合物，其有助于TRIM 5 α对HIV-1衣壳的亲合力，并且对于抑制感染是必不可少的;这些高阶自缔合复合物依赖于完整的B-box 2结构域。尽管形成高阶自缔合复合物的能力类似于在内吞囊泡周围形成蛋白质阵列或笼的网格蛋白三聚体，但缺乏TRIM 5 α在HIV-1核心周围组装类似类型结构的能力的证据。Ganser-Pornillos、Ganrasekaran及其同事最近的工作已经证明了限制因子TRIM 5 alpha通过在病毒衣壳表面形成六边形阵列来“笼住”或“网住”HIV-1核心的能力[1]。这种六边形阵列在设计上与网格蛋白包被的内吞囊泡表面上的网格蛋白三聚体形成的阵列惊人地相似。这一显著的发现代表了我们对限制因子TRIM 5 α理解的重要进展，并表明TRIM 5 α笼住HIV-1核心以终止感染。本说明讨论这一发现的影响。
The potent HIV-1 inhibitor TRIM5 alpha blocks HIV-1 infection by accelerating the uncoating of HIV-1. TRIM5 alpha is known to form higher-order self-association complexes that contribute to the avidity of TRIM5 alpha for the HIV-1 capsid, and are essential to inhibit infection; these higher-order self-association complexes are dependent upon an intact B-box 2 domain. Even though the ability to form higher-order self-association complexes resembles the clathrin triskelion that forms a protein array, or cage, around the endocytic vesicle, evidence for the ability of TRIM5 alpha to assemble a similar type of structure surrounding the HIV-1 core has been lacking. Recent work by Ganser-Pornillos, Chandrasekaran and colleagues has now demonstrated the ability of the restriction factor TRIM5 alpha to "cage" or "net" the HIV-1 core by forming an hexagonal array on the surface of the viral capsid [1]. This hexagonal array is strikingly similar in design to the array formed by the clathrin triskelion on the surface of the clathrin-coated endocytic vesicle. This remarkable finding represents an important advance on our understanding of the restriction factor TRIM5 alpha, and suggests that TRIM5 alpha cages the HIV-1 core in order to terminate infection. The present note discusses the implications of this discovery.