Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels

	Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels
	Lv SQ(吕守琴); An HL; Zhang HL; Long M(龙勉); Long M(龙勉)
刊名	MOLECULAR NEUROBIOLOGY
	2016
通讯作者邮箱	zhanghl@hebmu.edu.cn ; mlong@imech.ac.cn
卷号	53 期号:9 页码:5948-5961
关键词	Inward-rectifier potassiumchannel Molecular dynamicssimulations Conformationalchange Patchclamp Structure-function relationship
ISSN号	0893-7648
通讯作者	Long, M (reprint author), Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China. ; Long, M (reprint author), Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China. ; Long, M (reprint author), Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing 100190, Peoples R China. ; Zhang, HL (reprint author), Hebei Med Univ, Key Lab Neural & Vasc Biol, Minist Educ, Key Lab Pharmacol & Toxicol New Drug,Dept Pharmac, Shijiazhuang 050017, Hebei Province, Peoples R China.
产权排序	[Lu, Shouqin; Long, Mian] Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China; [Lu, Shouqin; Long, Mian] Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China; [Lu, Shouqin; Long, Mian] Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing 100190, Peoples R China; [An, Hailong] Hebei Univ Technol, Inst Biophys, Sch Sci, Key Lab Mol Biophys, Tianjin 300401, Hebei Province, Peoples R China; [Zhang, Hailin] Hebei Med Univ, Key Lab Neural & Vasc Biol, Minist Educ, Key Lab Pharmacol & Toxicol New Drug,Dept Pharmac, Shijiazhuang 050017, Hebei Province, Peoples R China
中文摘要	The effect of the conserved Leu/Ile site in the CD loop on the gating dynamics of Kir channels and corresponding micro-structural mechanism remains unclear. Molecular dynamics simulations were performed to investigate the structural mechanism of chicken Kir2.2. Compared to WT, the I223L mutant channel bound to PIP2 more strongly, was activated more rapidly, and maintained the activation state more stably after PIP2 dissociation. Cellular electrophysiology assays of mouse Kir2.1 and human Kir2.2 indicated that, consistent with simulations, the Leu residue increased the channel responses to PIP2 through increased binding affinity and faster activation kinetics, and the deactivation kinetics decreased upon PIP2 inhibition. The Ile residue induced the opposite responses. This difference was attributed to the distinct hydrophobic side chain symmetries of Leu and Ile; switching between these residues caused the interaction network to redistribute and offered effective conformation transduction in the Leu systems, which had more rigid and independent subunits.
分类号	一类
类目[WOS]	Neurosciences
研究领域[WOS]	Neurosciences & Neurology
关键词[WOS]	Inward-rectifier potassiumchannel ; Molecular dynamicssimulations ; Conformationalchange ; Patchclamp ; Structure-function relationship
收录类别	SCI
原文出处	http://dx.doi.org/10.1007/s12035-015-9466-x
语种	英语
WOS记录号	WOS:000387231300012
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/59686]
专题	力学研究所_国家微重力实验室
推荐引用方式 GB/T 7714	Lv SQ,An HL,Zhang HL,et al. Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels[J]. MOLECULAR NEUROBIOLOGY,2016,53(9):5948-5961.
APA	吕守琴,An HL,Zhang HL,龙勉,&Long M.(2016).Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels.MOLECULAR NEUROBIOLOGY,53(9),5948-5961.
MLA	吕守琴,et al."Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels".MOLECULAR NEUROBIOLOGY 53.9(2016):5948-5961.