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典型文献
The allosteric gating mechanism of the MthK channel
文献摘要:
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.
文献关键词:
作者姓名:
Fenghui Guan;Tianyu Li;Wei Dong;Rui Guo;Hao Chai;Zhiqiu Chen;Zhong Ren;Yang Li;Sheng Ye
作者机构:
Frontiers Science Center for Synthetic Biology(Ministry of Education),Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures,School of Life Sciences,Tianjin University,Tianjin 300072,China;The Cancer Hospital of the University of Chinese Academy of Sciences,Institute of Basic Medicine and Cancer(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China;State Key Laboratory of Drug Research and Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China;Life Sciences Institute,Zhejiang University,Hangzhou 310058,China;Department of Logistics,Tianjin University,Tianjin 300072,China;Department of Chemistry,University of Illinois at Chicago,Chicago,IL 60607,USA;Renz Research Inc.,Westmont,IL 60559,USA;National Clinical Research Center for Aging and Medicine,Huashan Hospital,Fudan University,Shanghai 200040,China
引用格式:
[1]Fenghui Guan;Tianyu Li;Wei Dong;Rui Guo;Hao Chai;Zhiqiu Chen;Zhong Ren;Yang Li;Sheng Ye-.The allosteric gating mechanism of the MthK channel)[J].国家科学评论(英文版),2022(08):26-37
A类:
MthK,Allostery,Ca2+ion,Ca2+affinity
B类:
allosteric,gating,mechanism,fundamental,element,during,response,appropriate,stimulus,by,which,events,occurring,one,are,transmitted,distal,sites,regulate,activity,To,address,how,binding,first,eight,chemically,identical,subunits,facilitates,other,gated,K+channel,containing,conserved,ligand,RCK,domain,analysed,large,collection,structures,performed,corresponding,thermodynamic,electrophysiological,measurements,These,structural,functional,studies,led,conclude,that,conformations,alternate,between,two,quaternary,states,exhibit,significant,differences,We,further,propose,model,cascade,connect,initial,final,changes,open,conduction,pore,This,mechanical,reveals,exquisite,design,achieves,could,general,relevance,action,channels
AB值:
0.543948
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