TRIM5 structure, HIV-1 capsid recognition, and innate immune signaling.

TRIM5 structure, HIV-1 capsid recognition, and innate immune signaling.
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DOI:
10.1016/j.coviro.2012.02.003
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发表时间:
2012-04
影响因子:
5.9
通讯作者:
Luban, Jeremy
Luban, Jeremy
中科院分区:
医学2区
文献类型:
--
作者:
Gruetter, Markus G.;Luban, Jeremy

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TRIM 5是一种限制因子,在病毒体核心进入细胞质后不久就阻断逆转录病毒感染。限制活性通过识别包裹病毒基因组RNA的衣壳蛋白晶格靶向病毒粒子核心。与许多TRIM家族成员一样,TRIM 5具有RING、B-box和卷曲螺旋结构域。作为E3泛素连接酶,TRIM 5与异源二聚体E2(UBC 13/UEV 1A)协作以激活TAK 1(MAP 3 K7)激酶、NF-κB和AP-1信号传导以及炎性细胞因子和趋化因子的转录。TAK 1、UBC 13和UEV 1A均有助于TRIM 5介导的逆转录病毒限制活性。TRIM 5的羧基末端PRYSPRY或亲环蛋白结构域与逆转录病毒衣壳晶格的相互作用刺激TRIM 5形成互补晶格,大大增加了TRIM 5 E3活性和宿主细胞信号转导。对TRIM 5的结构和生化研究为先天免疫系统如何检测HIV-1和其他逆转录病毒的独特分子特征打开了一扇急需的窗口。
TRIM5 is a restriction factor that blocks retrovirus infection soon after the virion core enters the cell cytoplasm. Restriction activity is targeted to the virion core via recognition of the capsid protein lattice that encases the viral genomic RNA. In common with all of the many TRIM family members, TRIM5 has RING, B-box, and coiled-coil domains. As an E3 ubiquitin ligase TRIM5 cooperates with the heterodimeric E2, UBC13/UEV1A, to activate the TAK1 (MAP3K7) kinase, NF-κB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines. TAK1, UBC13, and UEV1A all contribute to TRIM5-mediated retrovirus restriction activity. Interaction of the carboxy-terminal PRYSPRY or cyclophilin domains of TRIM5 with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction. Structural and biochemical studies on TRIM5 have opened a much needed window on how the innate immune system detects the distinct molecular features of HIV-1 and other retroviruses.
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