Structural and biochemical studies of RIG-I antiviral signaling

	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.