The allosteric gating mechanism of the MthK channel

doi:10.1093/nsr/nwac072

	The allosteric gating mechanism of the MthK channel
	Guan, Fenghui 9,10; Li, Tianyu 6,7,8; Dong, Wei 5; Guo, Rui 4; Chai, Hao 6,7,8; Chen, Zhiqiu 6; Ren, Zhong 2,3; Li, Yang 1,6,7,8; Ye, Sheng 5,10
刊名	NATIONAL SCIENCE REVIEW
	2022-09-03
卷号	9
关键词	ion channel allosteric gating mechanism protein structural data analysis
ISSN号	2095-5138
DOI	10.1093/nsr/nwac072
通讯作者	Ren, Zhong(zren@uic.edu) ; Li, Yang(yangli@mail.shcnc.ac.cn) ; Ye, Sheng(sye@tju.edu.cn)
英文摘要	Allostery is a fundamental element during channel gating in response to an appropriate stimulus by which events occurring at one site are transmitted to distal sites to regulate activity. To address how binding of the first Ca2+ ion at one of the eight chemically identical subunits facilitates the other Ca2+-binding events in MthK, a Ca2+-gated K+ channel containing a conserved ligand-binding RCK domain, we analysed a large collection of MthK structures and performed the corresponding thermodynamic and electrophysiological measurements. These structural and functional studies led us to conclude that the conformations of the Ca2+-binding sites alternate between two quaternary states and exhibit significant differences in Ca2+ affinity. We further propose an allosteric model of the MthK-gating mechanism by which a cascade of structural events connect the initial Ca2+-binding to the final changes of the ring structure that open the ion-conduction pore. This mechanical model reveals the exquisite design that achieves the allosteric gating and could be of general relevance for the action of other ligand-gated ion channels containing the RCK domain.
资助项目	Ministry of Science and Technology of China[2020YFA0908500] ; National Natural Science Foundation of China[31971127] ; National Natural Science Foundation of China[31900041] ; National Natural Science Foundation of China[31371066] ; National Natural Science Foundation of China[31671049] ; Fundamental Research Funds for the Central Universities
WOS关键词	K+-CHANNEL ; RCK DOMAIN ; CRYSTAL-STRUCTURE ; BK CHANNELS ; ACTIVATION ; SUBUNIT ; RING ; COOPERATIVITY
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000849495900001
资助机构	Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/131916]
专题	中国科学院合肥物质科学研究院
通讯作者	Ren, Zhong; Li, Yang; Ye, Sheng
作者单位	1.Fudan Univ, Natl Clin Res Ctr Aging & Med, Huashan Hosp, Shanghai 200040, Peoples R China 2.Renz Res Inc, Westmont, IL 60559 USA 3.Univ Illinois, Dept Chem, Chicago, IL 60607 USA 4.Tianjin Univ, Dept Logist, Tianjin 300072, Peoples R China 5.Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 9.Chinese Acad Sci, Canc Hosp, Univ Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Peoples R China 10.Tianjin Univ, Sch Life Sci, Tianjin Key Lab Funct & Applicat Biol Macromol St, Minist Educ,Frontiers Sci Ctr Synthet Biol, Tianjin 300072, Peoples R China
推荐引用方式 GB/T 7714	Guan, Fenghui,Li, Tianyu,Dong, Wei,et al. The allosteric gating mechanism of the MthK channel[J]. NATIONAL SCIENCE REVIEW,2022,9.
APA	Guan, Fenghui.,Li, Tianyu.,Dong, Wei.,Guo, Rui.,Chai, Hao.,...&Ye, Sheng.(2022).The allosteric gating mechanism of the MthK channel.NATIONAL SCIENCE REVIEW,9.
MLA	Guan, Fenghui,et al."The allosteric gating mechanism of the MthK channel".NATIONAL SCIENCE REVIEW 9(2022).