Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains

doi:10.1016/j.immuni.2021.09.008

	Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains
	Song, Bin 2; Chen, Yun 7,10; Liu, Xin 2; Yuan, Fei 2; Tan, Eddie Yong Jun 5,6; Lei, Yixuan 2; Song, Ning 2; Han, Yinqi 2; Pascal, Bruce D.9; Griffin, Patrick R.8
刊名	IMMUNITY
	2021-10-12
卷号	54 期号:10 页码:2218-+
ISSN号	1074-7613
DOI	10.1016/j.immuni.2021.09.008
通讯作者	Zheng, Jie(jzheng@simm.ac.cn)
英文摘要	The RNA sensor MDA5 recruits the signaling adaptor MAVS to initiate type I interferon signaling and downstream antiviral responses, a process that requires K63-linked polyubiquitin chains. Here, we examined the mechanisms whereby K63-polyUb chain regulate MDA5 activation. Only long unanchored K63-polyUb(n) (n >= 8) could mediate tetramerization of the caspase activation and recruitment domains of MDA5 (MDA5CARDs). Cryoelectron microscopy structures of a polyUb(13)-bound (MDA5)CARDs tetramer and a polyUb(11)-bound (MDA5)CARDs-(MAVS)CARD assembly revealed a tower-like formation, wherein eight Ubs tethered along the outer rim of the helical shell, bridging (MDA5)CARDs and (MAVS)CARD tetramers into proximity. ATP binding and hydrolysis promoted the stabilization of RNA-bound MDA5 prior to MAVS activation via allosteric effects on CARDs-polyUb complex. Abundant ATP prevented basal activation of apo MDA5. Our findings reveal the ordered assembly of aMDA5 signaling complex competent to recruit and activate MAVS and highlight differences with RIG-I in terms of CARD orientation and Ub sensing that suggest different abilities to induce antiviral responses.
资助项目	Shanghai Institute of Material Medica ; 100 Talents program of the Chinese Academy of Sciences, National Natural Science Foundation of China[81971538] ; Shanghai PuJiang Talent program[PJ20190001389] ; Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 1[2018-T1-002-010] ; Singapore Ministry of Health's National Medical Research Council[NMRC/OFIRG/0075/2018]
WOS关键词	RIG-I ; STRUCTURAL BASIS ; ACTIVATION ; RECOGNITION ; ADAR1 ; MDA5 ; SELF ; MUTATIONS ; RESPONSES ; IMMUNITY
WOS研究方向	Immunology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000706854100011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298481]
专题	中国科学院上海药物研究所
通讯作者	Zheng, Jie
作者单位	1.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res,Ctr Chem Biol, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 4.Nanyang Technol Univ, Lee Kong Chian Sch Med, EMB 03-07,59 Nanyang Dr, Singapore 636921, Singapore 5.Nanyang Technol Univ, NTU Inst Struct Biol, EMB 06-01,59 Nanyang Dr, Singapore 636921, Singapore 6.Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 636921, Singapore 7.NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA 8.Scripps Res Inst, Dept Mol Med, Jupiter, FL 33458 USA 9.Omics Informat LLC, Honolulu, HI 96813 USA 10.BeiGene Shanghai Co Ltd, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Song, Bin,Chen, Yun,Liu, Xin,et al. Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains[J]. IMMUNITY,2021,54(10):2218-+.
APA	Song, Bin.,Chen, Yun.,Liu, Xin.,Yuan, Fei.,Tan, Eddie Yong Jun.,...&Zheng, Jie.(2021).Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains.IMMUNITY,54(10),2218-+.
MLA	Song, Bin,et al."Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains".IMMUNITY 54.10(2021):2218-+.