Structural and biochemical studies of RIG-I antiviral signaling | |
Feng, M; Ding, ZY; Xu, L; Kong, LL; Wang, WJ; Jiao, S; Shi, ZB; Greene, MI; Cong, Y; Zhou, ZC | |
刊名 | PROTEIN & CELL |
2013 | |
卷号 | 4期号:2页码:142-154 |
关键词 | RIG-I MAVS antiviral signaling polyubiquitin phosphorylation |
通讯作者 | Cong, Y (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,cong@sibcb.ac.cn |
英文摘要 | Retinoic acid-inducible gene I (RIG-I) is an important pattern recognition receptor that detects viral RNA and triggers the production of type-I interferons through the downstream adaptor MAVS (also called IPS-1, CARDIF, or VISA). A series of structural studies have elaborated some of the mechanisms of dsRNA recognition and activation of RIG-I. Recent studies have proposed that K63-linked ubiquitination of, or unanchored K63-linked polyubiquitin binding to RIG-I positively regulates MAVS-mediated antiviral signaling. Conversely phosphorylation of RIG-I appears to play an inhibitory role in controlling RIG-I antiviral signal transduction. Here we performed a combined structural and biochemical study to further define the regulatory features of RIG-I signaling. ATP and dsRNA binding triggered dimerization of RIG-I with conformational rearrangements of the tandem CARD domains. Full length RIG-I appeared to form a complex with dsRNA in a 2:2 molar ratio. Compared with the previously reported crystal structures of RIG-I in inactive state, our electron microscopic structure of full length RIG-I in complex with blunt-ended dsRNA, for the first time, revealed an exposed active conformation of the CARD domains. Moreover, we found that purified recombinant RIG-I proteins could bind to the CARD domain of MAVS independently of dsRNA, while S8E and T170E phosphorylation-mimicking mutants of RIG-I were defective in binding E3 ligase TRIM25, unanchored K63-linked polyubiquitin, and MAVS regardless of dsRNA. These findings suggested that phosphorylation of RIG inhibited downstream signaling by impairing RIG-I binding with polyubiquitin and its interaction with MAVS. |
学科主题 | Cell Biology |
类目[WOS] | Cell Biology |
关键词[WOS] | INNATE IMMUNE-RESPONSE ; DOUBLE-STRANDED-RNA ; UBIQUITIN LIGASE ; ELECTRON-MICROSCOPY ; NEGATIVE REGULATION ; ADAPTER PROTEIN ; HIGH-RESOLUTION ; VIRAL-RNA ; RECOGNITION ; ACTIVATION |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000316228300006 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/339] |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Feng, M,Ding, ZY,Xu, L,et al. Structural and biochemical studies of RIG-I antiviral signaling[J]. PROTEIN & CELL,2013,4(2):142-154. |
APA | Feng, M.,Ding, ZY.,Xu, L.,Kong, LL.,Wang, WJ.,...&Zhou, ZC.(2013).Structural and biochemical studies of RIG-I antiviral signaling.PROTEIN & CELL,4(2),142-154. |
MLA | Feng, M,et al."Structural and biochemical studies of RIG-I antiviral signaling".PROTEIN & CELL 4.2(2013):142-154. |
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