The B30.2(SPRY) domain of the retroviral restriction factor TRIM5α exhibits line age-specific length and sequence variation in primates
The B30.2(SPRY) domain of the retroviral restriction factor TRIM5α exhibits line age-specific length and sequence variation in primates
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DOI：
10.1128/jvi.79.10.6111-6121.2005
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发表时间：
2005-05-01
影响因子：
5.4
通讯作者：
Sodroski, J
中科院分区：
文献类型：
--
作者：
Song, BW;Gold, B;Sodroski, J
三部分基序(Trim)蛋白由环结构域、B-box 2结构域和螺旋卷曲结构域组成。一些TRIM蛋白，如TRIM5α，也具有羧基末端B30.2(Spry)结构域，并定位于细胞质小体。TRIM5a最近被证明介导了对逆转录病毒的先天细胞内抵抗，这种活性依赖于B30.2结构域的完整性，特别是灵长类物种。对与TRIM5相关的几个TRIM蛋白的序列进行了研究，发现B30.2结构域存在四个可变区(v1、v2、v3和v4)。通过扩增、克隆和测序非人类灵长类动物的TRIM5同源基因，分析了TRIM5α基因的物种特异性变异。在东半球灵长类和新大陆猕猴中，TRIM5αB30.2 v1区和v3区发生了谱系特异性扩展和顺序复制。我们观察到了与这些特定的B30.2结构域可变元件相邻的指示选择的替换模式。这些结果表明，在灵长类动物的进化过程中，偶尔的复杂变化被纳入到TRIM5a B30.2结构域的离散时间点。根据灵长类基因组中出现的特定内源性逆转录病毒，其中一些时间点对应于灵长类接触逆转录病毒感染的时期。这一结果与TRIM5α在对抗逆转录病毒的先天免疫中的作用是一致的。
Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5 alpha, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5a has recently been shown to mediate innate intracellular resistance to retroviruses, an activity dependent on the integrity of the B30.2 domain, in particular primate species. An examination of the sequences of several TRIM proteins related to TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the B30.2 domain. Species-specific variation in TRIM5 alpha was analyzed by amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5 alpha B30.2 v1 region in Old World primates and in v3 in New World monkeys. We observed substitution patterns indicative of selection bordering these particular B30.2 domain variable elements. These results suggest that occasional, complex changes were incorporated into the TRIM5a B30.2 domain at discrete time points during the evolution of primates. Some of these time points correspond to periods during which primates were exposed to retroviral infections, based on the appearance of particular endogenous retroviruses in primate genomes. The results are consistent with a role for TRIM5 alpha in innate immunity against retroviruses.