Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel

doi:10.1016/j.celrep.2021.110025

KMS > 免疫化学研究所 > 特聘教授组 > Roger D. Kornberg组

	Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel
	Yu, Xiafe 1,2; Xie, Yuan 3,4; Zhang, Xiaokang 5,6,7; Ma, Cheng 8; Liu, Likun 1,2; Zhen, Wenxuan 9,10; Xu, Lingyi 3,4; Zhang, Jianmin 1,2; Liang, Yan 11,12; Zhao, Lixia13 ; Gao, Xiuxia13 ; Yu, Peilin 11,12; Luo, Jianhong 14; Jiang, Lin-Hua 15,16; Nie, Yan 14; Yang, Fan 9,10; Guo, Jiangtao 3,4; Yang, Wei 1,2
	2021-11-16
发表期刊	CELL REPORTS (IF:7.5[JCR-2023],8.5[5-Year])
ISSN	2211-1247
卷号	37 期号:7
DOI	10.1016/j.celrep.2021.110025
摘要	Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca2+, warm temperature, and oxidative stress. It is critically involved in physiological and pathological processes ranging from inflammation to stroke to neurodegeneration. At present, the channel's gating and ion permeation mechanisms, such as the location and identity of the selectivity filter, remain ambiguous. Here, we report the cryo-electron microscopy (cryo-EM) structure of human TRPM2 in nanodisc in the ligand-free state. Cryo-EM map-guided computational modeling and patch-clamp recording further identify a quadruple-residue motif as the ion selectivity filter, which adopts a restrictive conformation in the closed state and acts as a gate, profoundly contrasting with its widely open conformation in the Nematostella vectensis TRPM2. Our study reveals the gating of human TRPM2 by the filter and demonstrates the feasibility of using cryo-EM in conjunction with computational modeling and functional studies to garner structural information for intrinsically dynamic but functionally important domains.
收录类别	SCIE
语种	英语
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000720350900001
出版者	CELL PRESS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/133151
专题	免疫化学研究所_特聘教授组_结构生物化学实验室免疫化学研究所_公共科研平台_分析化学平台
通讯作者	Yang, Fan; Guo, Jiangtao; Yang, Wei
作者单位	1.Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Biophys, Hangzhou 310058, Zhejiang, Peoples R China; 2.Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Neurosurg, Hangzhou 310058, Zhejiang, Peoples R China; 3.Zhejiang Univ, Sch Med, Shaw Hosp, Dept Biophys, Hangzhou 310058, Peoples R China; 4.Zhejiang Univ, Sch Med, Shaw Hosp, Dept Pathol Sir Run 14, Hangzhou 310058, Peoples R China; 5.Zhejiang Univ, Ctr Cryoelectron Microscopy, Sch Med, Hangzhou 310058, Peoples R China; 6.Chinese Acad Sci, Shenzhen Inst Adv Technol, Brain Cognit & Brain Dis Inst, Interdisciplinary Ctr Brain Informat,Fac Life & H, Shenzhen 518055, Guangdong, Peoples R China; 7.Shenzhen Hong Kong Inst Brain Sci Shenzhen Fundam, Shenzhen 518055, Guangdong, Peoples R China; 8.Zhejiang Univ, Cofacil Ctr, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China; 9.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Biophys, Hangzhou 310058, Zhejiang, Peoples R China; 10.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Kidney Dis Ctr, Hangzhou 310058, Zhejiang, Peoples R China; 11.Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Toxicol, Hangzhou 310058, Zhejiang, Peoples R China; 12.Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Med Oncol, Hangzhou 310058, Zhejiang, Peoples R China; 13.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China; 14.Zhejiang Univ, Key Lab Med Neurobiol, Zhejiang Prov Key Lab Neurobiol, Minist Hlth China,Dept Neurobiol,Sch Med, Hangzhou 310058, Zhejiang, Peoples R China; 15.Univ Leeds, Fac Biol Sci, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England; 16.Xinxiang Med Univ, Dept Physiol & Neurobiol, Sino UK Joint Lab Brain Funct & Injury, Xinxiang, Henan, Peoples R China
推荐引用方式 GB/T 7714	Yu, Xiafe,Xie, Yuan,Zhang, Xiaokang,et al. Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel[J]. CELL REPORTS,2021,37(7).
APA	Yu, Xiafe.,Xie, Yuan.,Zhang, Xiaokang.,Ma, Cheng.,Liu, Likun.,...&Yang, Wei.(2021).Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel.CELL REPORTS,37(7).
MLA	Yu, Xiafe,et al."Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel".CELL REPORTS 37.7(2021).