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

	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
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2012-12-01
通讯作者邮箱	mlong@imech.ac.cn;z.hailin@yahoo.com; delogothetis@vcu.edu
卷号	287 期号:50 页码:42278-42287
关键词	Rectifier K+ Channels Beta-Gamma-Subunits Potassium Channels Crystal-Structure G-Proteins Structural Basis Voltage-Sensor PIP2 Activation Dynamics
ISSN号	0021-9258
通讯作者	Long, M ; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China.
产权排序	[Lu, Shou-Qin;Long, Mian] Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China; [Lu, Shou-Qin; Long, Mian] Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China; [An, Hai-Long; Meng, Xuan-Yu; Cui, Meng; Logothetis, Diomedes E.] Virginia Commonwealth Univ, Sch Med, Dept Physiol & Biophys, Richmond, VA 23298 USA; [An, Hai-Long; Li, Jun-Wei; Zhan, Yong] Hebei Univ Technol, Inst Biophys, Sch Sci, Tianjin 300401, Peoples R China; [Zhang, Hai-Lin] Hebei Med Univ, Key Lab Pharmacol & Toxicol New Drug, Key Lab Neural & Vasc Biol, Minist Educ,Dept Pharmacol, Shijiazhuang 050017, Hebei Province, Peoples R China
合作状况	国际
中文摘要	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.
学科主题	生物力学
分类号	二类/Q2
收录类别	SCI ; EI
资助信息	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.).
原文出处	http://dx.doi.org/10.1074/jbc.M112.418640
语种	英语
WOS记录号	WOS:000312103000063
公开日期	2013-01-18
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/46602]
专题	力学研究所_国家微重力实验室
通讯作者	Long, M
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.,...&Long, M.(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.