Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism

doi:10.1371/journal.pbio.1000151

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism
	Yang, Huaiyu 2; Yu, Ye 1,3; Li, Wei-Guang 1,3; Yu, Fang 1,3; Cao, Hui 1,3; Xu, Tian-Le 1,3; Jiang, Hualiang2,4
刊名	PLOS BIOLOGY
	2009-07
卷号	7 期号:7
ISSN号	1544-9173
DOI	10.1371/journal.pbio.1000151
文献子类	Article
英文摘要	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
资助项目	State Key Program of Basic Research of China[2009CB918502] ; State Key Program of Basic Research of China[2006CB500803] ; China Postdoctoral Science Foundation[20080440095] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[20720102040] ; National Natural Science Foundation of China[30830035] ; National Natural Science Foundation of China[30700145] ; National Natural Science Foundation of China[30621062]
WOS关键词	NORMAL-MODE ANALYSIS ; NICOTINIC ACETYLCHOLINE-RECEPTOR ; EPITHELIAL NA+ CHANNEL ; SINGLE-PARAMETER ; PROTEINS ; CONTRIBUTES ; FLEXIBILITY ; SELECTIVITY ; PERMEATION ; MOTIONS
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000268405700005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279204]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yang, Huaiyu
作者单位	1.Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China; 4.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Yang, Huaiyu,Yu, Ye,Li, Wei-Guang,et al. Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism[J]. PLOS BIOLOGY,2009,7(7).
APA	Yang, Huaiyu.,Yu, Ye.,Li, Wei-Guang.,Yu, Fang.,Cao, Hui.,...&Jiang, Hualiang.(2009).Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism.PLOS BIOLOGY,7(7).
MLA	Yang, Huaiyu,et al."Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism".PLOS BIOLOGY 7.7(2009).