The allosteric gating mechanism of the MthK channel
文献类型：期刊论文
| 作者 | Guan, Fenghui9,10; Li, Tianyu6,7,8; Dong, Wei5; Guo, Rui4; Chai, Hao6,7,8; Chen, Zhiqiu6; Ren, Zhong2,3; Li, Yang1,6,7,8 ; Ye, Sheng5,10
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| 刊名 | NATIONAL SCIENCE REVIEW
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| 出版日期 | 2022-09-03 |
| 卷号 | 9期号:8页码:12 |
| 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. |
| WOS关键词 | K+-CHANNEL ; RCK DOMAIN ; CRYSTAL-STRUCTURE ; BK CHANNELS ; ACTIVATION ; SUBUNIT ; RING ; COOPERATIVITY |
| 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研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000849495900001 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302144]  |
| 专题 | 新药研究国家重点实验室 |
| 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(8):12. |
| 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(8),12. |
| MLA | Guan, Fenghui,et al."The allosteric gating mechanism of the MthK channel".NATIONAL SCIENCE REVIEW 9.8(2022):12. |
入库方式： OAI收割
来源：上海药物研究所
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