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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.
2012-12-01
发表期刊JOURNAL OF BIOLOGICAL CHEMISTRY
卷号287期号:50页码:42278-42287
ISSN0021-9258
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
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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
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被引频次:13[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
专题国家微重力实验室
通讯作者Long, M; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China.
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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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