Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1301 Morris Park-Price Center 501, Bronx, NY 10461, USA.
Virology. 2014 Jan 5;448:217-28. doi: 10.1016/j.virol.2013.10.012. Epub 2013 Oct 31.
The PRYSPRY domain of TRIM5α provides specificity and the capsid recognition motif to retroviral restriction. Restriction of HIV-1 by rhesus TRIM5α (TRIM5αrh) has been correlated to its ability to bind to the HIV-1 core, suggesting that capsid binding is required for restriction. This work explores whether the PRYSPRY domain of TRIM5αrh exhibits an additional function besides binding to the HIV-1 core. Using our recently described structure of the PRYSPRY domain, we performed an exhaustive structure-function study of the surface and interior residues of the PRYSPRY domain. Testing retroviral restriction and capsid binding of an extensive collection of 60 TRIM5αrh PRYSPRY variants revealed that binding is necessary but not sufficient for restriction. In support of this hypothesis, we showed that some human tripartite motif proteins bind the HIV-1 capsid but do not restrict HIV-1 infection, such as human TRIM6 and TRIM34. Overall this work suggested that the PRYSPRY domain serves an unknown function, distinct from the binding of TRIM5αrh to the HIV-1 core, to block HIV-1 infection.
TRIM5α 的 PRYSPRY 结构域提供了对逆转录病毒的特异性和衣壳识别基序的限制。恒河猴 TRIM5α（TRIM5αrh）对 HIV-1 的限制与其结合 HIV-1 核心的能力有关，这表明衣壳结合是限制所必需的。这项工作探讨了 TRIM5αrh 的 PRYSPRY 结构域除了与 HIV-1 核心结合之外是否还具有其他功能。使用我们最近描述的 PRYSPRY 结构域结构，我们对 PRYSPRY 结构域的表面和内部残基进行了详尽的结构功能研究。测试了广泛的 60 种 TRIM5αrh PRYSPRY 变体的逆转录病毒限制和衣壳结合，结果表明结合是限制所必需的，但不是充分的。为了支持这一假设，我们表明一些人类三联体基序蛋白结合 HIV-1 衣壳但不限制 HIV-1 感染，例如人类 TRIM6 和 TRIM34。总的来说，这项工作表明 PRYSPRY 结构域具有未知的功能，与 TRIM5αrh 结合 HIV-1 核心不同，可阻止 HIV-1 感染。
