The TRIM5α B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association
The TRIM5α B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association
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DOI：
10.1128/jvi.01548-08
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发表时间：
2008-12-01
影响因子：
5.4
通讯作者：
Sodroski, Joseph
中科院分区：
文献类型：
--
作者：
Li, Xing;Sodroski, Joseph
逆转录病毒限制因子TRIM5 α在病毒进入细胞后不久阻断一系列逆转录病毒的感染。TRIM5 α由RING、B-box 2、coil -coil和B30.2（SPRY）结构域组成。B-box - 2结构域是逆转录病毒被TRIM5 α限制所必需的，但其具体功能尚不清楚。我们在这里表明，B-box 2结构域介导TRIM5 α rh低聚物的高阶自结合。这种自我结合增加了TRIM5 α与逆转录病毒衣壳结合的效率，从而增强了对逆转录病毒感染的限制。B-box 2结构域对TRIM5 α与逆转录病毒衣壳协同结合的贡献解释了一些B-box 2 TRIM5 α突变体所表现出的限制性表型的条件性质；当B30.2（SPRY）结构域介导的衣壳与逆转录病毒衣壳的相互作用较弱时，B-box 2介导的自结合对衣壳结合的增强是必要的。因此，B-box 2依赖的高阶自结合和B30.2（SPRY）依赖的衣壳结合代表了互补机制，从而可以实现衣壳结合的TRIM5 α蛋白的足够密集的阵列。
The retroviral restriction factor, TRIM5 alpha, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5 alpha consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The B-box 2 domain is essential for retrovirus restriction by TRIM5 alpha, but its specific function is unknown. We show here that the B-box 2 domain mediates higher-order self-association of TRIM5 alpha rh oligomers. This self-association increases the efficiency of TRIM5 alpha binding to the retroviral capsid, thus potentiating restriction of retroviral infection. The contribution of the B-box 2 domain to cooperative TRIM5 alpha association with the retroviral capsid explains the conditional nature of the restriction phenotype exhibited by some B-box 2 TRIM5 alpha mutants; the potentiation of capsid binding that results from B-box 2-mediated self-association is essential for restriction when B30.2(SPRY) domain-mediated interactions with the retroviral capsid are weak. Thus, B-box 2-dependent higher-order self-association and B30.2(SPRY)-dependent capsid binding represent complementary mechanisms whereby sufficiently dense arrays of capsid-bound TRIM5 alpha proteins can be achieved.