The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels

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	The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels
	An HL; Lv SQ(吕守芹); Li JW; Meng XY; Zhan Y; Cui M; Long M(龙勉); Zhang HL; Logothetis DE; Long, M; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China.
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY
	2012-12-01
卷号	287 期号:50 页码:42278-42287
ISSN	0021-9258
摘要	Inwardly rectifying K+ (Kir) channels set the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP2. The molecular mechanism by which PIP2 regulates Kir channel gating is poorly understood. Here, we utilized a combination of computational and electrophysiological approaches to discern structural elements involved in regulating the PIP2-induced gating kinetics of Kir2 channels. We identify a novel role for the cytosolic GH loop. Mutations that directly or indirectly affect GH loop flexibility (e.g. V223L, E272G, D292G) increase both the on- and especially the off-gating kinetics. These effects are consistent with a model in which competing interactions between the CD and GH loops for the N terminus regulate the gating of the intracellular G loop gate.
关键词	Rectifier K++ Channels Beta-gamma-subunits Potassium Channels Crystal-structure G-proteins Structural Basis Voltage-sensor Pip2 Activation Dynamics
学科领域	生物力学
URL	查看原文
收录类别	SCI ; EI
语种	英语
WOS记录号	WOS:000312103000063
项目资助者	This work was supported, in whole or in part, by grant National Institutes of Health Grant HL059949 (to D.L.). This work was also supported by NSFC (National Natural Science Foundation of China) Grants 11145003 (to H.A.), 10975045 and C2009000029 (to Y.Z.), and 30730031 (to H.Z.) and by 973 Program Grants 2007CB512100 and C2009001104 (to H.Z.). Computations performed at VCU were supported by the Center for High Performance Computing (CHiPC) and by the National Institutes of Health Grant S10RR027411 (to M.C.).
课题组名称	NML分子-细胞生物力学与空间生命科学
论文分区	二类/Q2
引用统计	被引频次：18[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://dspace.imech.ac.cn/handle/311007/46602
专题	微重力重点实验室
通讯作者	Long, M; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China.
推荐引用方式 GB/T 7714	An HL,Lv SQ,Li JW,et al. The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287,50,:42278-42287.
APA	An HL.,Lv SQ.,Li JW.,Meng XY.,Zhan Y.,...&Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China..(2012).The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels.JOURNAL OF BIOLOGICAL CHEMISTRY,287(50),42278-42287.
MLA	An HL,et al."The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels".JOURNAL OF BIOLOGICAL CHEMISTRY 287.50(2012):42278-42287.

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