Identification of residues within the L2 region of rhesus TRIM5alpha that are required for retroviral restriction and cytoplasmic body localization.
Identification of residues within the L2 region of rhesus TRIM5alpha that are required for retroviral restriction and cytoplasmic body localization.
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DOI：
10.1016/j.virol.2010.06.015
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发表时间：
2010-09-15
期刊：
影响因子：
3.7
通讯作者：
Campbell EM
中科院分区：
文献类型：
--
作者：
Sastri J;O'Connor C;Danielson CM;McRaven M;Perez P;Diaz-Griffero F;Campbell EM
细胞内限制性因子TRIM5α以一种物种特异性的方式抑制许多逆转录病毒的感染。这种限制最典型的例子是来自恒河猴的TRIM5α蛋白（rhTRIM5α），它能有效地抑制HIV-1感染。TRIM5α定位于称为细胞质小体的蛋白的细胞质组装，尽管这些小体在逆转录病毒限制中发挥的作用尚不清楚。我们使用了一系列截断突变体来鉴定一个离散区域，该区域位于连接TRIM5α的线圈线圈和B30.2/PRYSPRY结构域的Linker2区域内，这是细胞质体定位所必需的。在全长rhTRIM5α的背景下，该区域的缺失取消了细胞质体定位。该区域残基的丙氨酸诱变确定了细胞质体定位和逆转录病毒限制所需的两段氨基酸。这项工作表明，介导TRIM5α定位到细胞质体的决定因素在逆转录病毒限制中起着必要的作用。
The intracellular restriction factor TRIM5α, inhibits infection by numerous retroviruses in a species-specific manner. The best characterized example of this restriction is the TRIM5α protein from rhesus macaques (rhTRIM5α), which potently inhibits HIV-1 infection. TRIM5α localizes to cytoplasmic assemblies of protein referred to as cytoplasmic bodies, though the role that these bodies play in retroviral restriction is unclear. We employed a series of truncation mutants to identify a discrete region, located within the Linker2 region connecting the coiled-coil and B30.2/PRYSPRY domains of TRIM5α, which is required for cytoplasmic body localization. Deletion of this region in the context of full-length rhTRIM5α abrogates cytoplasmic body localization. Alanine mutagenesis of the residues in this region identifies two stretches of amino acids that are required for both cytoplasmic body localization and retroviral restriction. This work suggests that the determinants that mediate TRIM5α localization to cytoplasmic bodies play a requisite role in retroviral restriction.
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影响因子：
6.7
作者：
Barr SD;Smiley JR;Bushman FD
通讯作者：
Bushman FD
DOI：
10.1038/nri2413
发表时间：
2008-11
期刊：
Nature reviews. Immunology
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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