Li Xing, Li Yuan, Stremlau Matthew, Yuan Wen, Song Byeongwoon, Perron Michel, Sodroski Joseph
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street-JFB 824, Boston, MA 02115, USA.
J Virol. 2006 Jul;80(13):6198-206. doi: 10.1128/JVI.00283-06.
Tripartite motif 5alpha (TRIM5alpha) restricts some retroviruses, including human immunodeficiency virus type 1 (HIV-1), from infecting the cells of particular species. TRIM5alpha is a member of the TRIM family of proteins, which contain RING, B-box, coiled-coil (CC), and, in some cases, B30.2(SPRY) domains. Here we investigated the abilities of domains from TRIM proteins (TRIM6, TRIM34, and TRIM21) that do not restrict HIV-1 infection to substitute for the domains of rhesus monkey TRIM5alpha (TRIM5alpha(rh)). The RING, B-box 2, and CC domains of the paralogous TRIM6 and TRIM34 proteins functionally replaced the corresponding TRIM5alpha(rh) domains, allowing HIV-1 restriction. By contrast, similar chimeras containing the components of TRIM21, a slightly more distant relative of TRIM5, did not restrict HIV-1 infection. The TRIM21 B-box 2 domain and its flanking linker regions contributed to the functional defectiveness of these chimeras. All of the chimeric proteins formed trimers. All of the chimeras that restricted HIV-1 infection bound the assembled HIV-1 capsid complexes. These results indicate that heterologous RING, B-box 2, and CC domains from related TRIM proteins can functionally substitute for TRIM5alpha(rh) domains.
三联基序蛋白5α(TRIM5α)可限制包括1型人类免疫缺陷病毒(HIV-1)在内的一些逆转录病毒感染特定物种的细胞。TRIM5α是TRIM蛋白家族的成员,该家族蛋白包含RING、B盒、卷曲螺旋(CC)结构域,在某些情况下还包含B30.2(SPRY)结构域。在此,我们研究了不限制HIV-1感染的TRIM蛋白(TRIM6、TRIM34和TRIM21)的结构域替代恒河猴TRIM5α(TRIM5α(rh))结构域的能力。同源的TRIM6和TRIM34蛋白的RING、B盒2和CC结构域在功能上替代了相应的TRIM5α(rh)结构域,从而实现对HIV-1的限制。相比之下,包含TRIM5关系稍远的亲属TRIM21成分的类似嵌合体则不能限制HIV-1感染。TRIM21的B盒2结构域及其侧翼连接区导致了这些嵌合体的功能缺陷。所有嵌合蛋白均形成三聚体。所有限制HIV-1感染的嵌合体都能结合组装好的HIV-1衣壳复合物。这些结果表明,来自相关TRIM蛋白的异源RING、B盒2和CC结构域在功能上可替代TRIM5α(rh)结构域。