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Title: Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism
Author: Yang, Huaiyu ; Yu, Ye ; Li, Wei-Guang ; Yu, Fang ; Cao, Hui ; Xu, Tian-Le(徐天乐) ; Jiang, Hualiang
Source: PLOS BIOLOGY
Issued Date: 2009
Volume: 7, Issue:7, Pages:e1000151-e1000152
Keyword: NORMAL-MODE ANALYSIS ; NICOTINIC ACETYLCHOLINE-RECEPTOR ; EPITHELIAL NA+ CHANNEL ; SINGLE-PARAMETER ; PROTEINS ; CONTRIBUTES ; FLEXIBILITY ; SELECTIVITY ; PERMEATION ; MOTIONS
Subject: Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
Corresponding Author: Yang, HY (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 200031, Peoples R China,tlxu@ion.ac.cn
English Abstract: The acid-sensing ion channel 1 (ASIC1) is a key receptor for extracellular protons. Although numerous structural and functional studies have been performed on this channel, the structural dynamics underlying the gating mechanism remains unknown. We used normal mode analysis, mutagenesis, and electrophysiological methods to explore the relationship between the inherent dynamics of ASIC1 and its gating mechanism. Here we show that a series of collective motions among the domains and subdomains of ASIC1 correlate with its acid-sensing function. The normal mode analysis result reveals that the intrinsic rotation of the extracellular domain and the collective motions between the thumb and finger induced by proton binding drive the receptor to experience a deformation from the extracellular domain to the transmembrane domain, triggering the channel pore to undergo "twist-to-open" motions. The movements in the transmembrane domain indicate that the likely position of the channel gate is around Leu440. These motion modes are compatible with a wide body of our complementary mutations and electrophysiological data. This study provides the dynamic fundamentals of ASIC1 gating. A
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1656
Appears in Collections:神经所(总)_期刊论文

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Yang, Huaiyu; Yu, Ye; Li, Wei-Guang; Yu, Fang; Cao, Hui; Xu, Tian-Le; Jiang, Hualiang.Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism,PLOS BIOLOGY,2009,7(7):e1000151-e1000152
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