DICP OpenIR
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
关键词Molecular Dynamic Simulation Connexin26 Ph Channel Gating
刊名BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
2012-05-01
DOI10.1016/j.bbamem.2011.12.027
1818期:5页:1148-1157
收录类别SCI
文章类型Article
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]MOLECULAR-DYNAMICS SIMULATIONS ; GAP-JUNCTION CHANNELS ; 3-DIMENSIONAL STRUCTURE ; PROTEIN CONNEXIN43 ; STRUCTURAL MODELS ; AMINO-TERMINUS ; PERMEABILITY ; TAURINE ; PORE ; AMINOSULFONATES
英文摘要Connexin (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.
语种英语
WOS记录号WOS:000302971100004
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/142864
专题中国科学院大连化学物理研究所
作者单位1.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
推荐引用方式
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.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Wang, Xia]的文章
[Xu, Xue]的文章
[Ma, Ming]的文章
百度学术
百度学术中相似的文章
[Wang, Xia]的文章
[Xu, Xue]的文章
[Ma, Ming]的文章
必应学术
必应学术中相似的文章
[Wang, Xia]的文章
[Xu, Xue]的文章
[Ma, Ming]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。