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pH-dependent channel gating in connexin26 hemichannels involves conformational changes in N-terminus
Wang, Xia1,2; Xu, Xue1,2; Ma, Ming1,2; Zhou, Wei1,2; Wang, Yonghua1,2; Yang, Ling3
KeywordMolecular Dynamic Simulation Connexin26 Ph Channel Gating
Source PublicationBIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
2012-05-01
DOI10.1016/j.bbamem.2011.12.027
Volume1818Issue:5Pages:1148-1157
Indexed BySCI
SubtypeArticle
WOS SubjectBiochemistry & Molecular Biology ; Biophysics
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics
WOS KeywordMOLECULAR-DYNAMICS SIMULATIONS ; GAP-JUNCTION CHANNELS ; 3-DIMENSIONAL STRUCTURE ; PROTEIN CONNEXIN43 ; STRUCTURAL MODELS ; AMINO-TERMINUS ; PERMEABILITY ; TAURINE ; PORE ; AMINOSULFONATES
AbstractConnexin (Cx) hemichannels controlling an exchange of ions and metabolites between the cytoplasm and extracellular milieu can be modulated by the variation of intracellular pH during physiological and pathological conditions. To address the mechanism by which the pH exerts its effect on hemichannels, we have performed two 100-ns molecular dynamics simulations of the Cx26 channel in both acidic and neutral states. The results show that: 1) transmembrane domains undergo clockwise motions around the pore axis under both acidic and neutral conditions, while extracellular segments keep stable. 2) Under neutral condition, Cx26 has a tightly closed configuration that occurs through the assembly of N-terminal helix (NTH) region. This shows a constriction formed by the interhelical interactions of Asp2 and Met1 from neighboring NTH, which shapes the narrowest segment (pore radius<2 angstrom) of the pore, preventing the passage of ions from the extracellular side. This indicates that Asp2 may act as a channel gate. 3) Under the acidic condition, the constriction is relieved by the protonation of Asp2 causing interruption of interhelical interactions, Cx26 has a flexibly opening pore (pore radius > 4.5 angstrom) around NTH region, allowing the passage of chloride ions unimpeded by the side-chain Asp2. While in the extracellular part two chloride ions interact with the side-chain Lys41 from three subunits. Finally, we provide a plausible mechanism of pH-dependent gating of hemichannel that involves protonation of the aspartic residues, suggesting that the pH sensitivity of hemichannel permeability is a sophisticated mechanism for cell regulating ion permeation. (C) 2011 Elsevier B.V. All rights reserved.
Language英语
WOS IDWOS:000302971100004
Citation statistics
Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/142864
Collection中国科学院大连化学物理研究所
Affiliation1.NW A&F Univ, Ctr Bioinformat, Yangling 712100, Shaanxi, Peoples R China
2.NW A&F Univ, Coll Life Sci, Yangling 712100, Shaanxi, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Liaoning, Peoples R China
Recommended Citation
GB/T 7714
Wang, Xia,Xu, Xue,Ma, Ming,et al. pH-dependent channel gating in connexin26 hemichannels involves conformational changes in N-terminus[J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES,2012,1818(5):1148-1157.
APA Wang, Xia,Xu, Xue,Ma, Ming,Zhou, Wei,Wang, Yonghua,&Yang, Ling.(2012).pH-dependent channel gating in connexin26 hemichannels involves conformational changes in N-terminus.BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES,1818(5),1148-1157.
MLA Wang, Xia,et al."pH-dependent channel gating in connexin26 hemichannels involves conformational changes in N-terminus".BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1818.5(2012):1148-1157.
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