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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.
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
2012-12-01
Volume287Issue:50Pages:42278-42287
ISSN0021-9258
AbstractInwardly 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.
KeywordRectifier K++ Channels Beta-gamma-subunits Potassium Channels Crystal-structure G-proteins Structural Basis Voltage-sensor Pip2 Activation Dynamics
Subject Area生物力学
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Indexed BySCI ; EI
Language英语
WOS IDWOS:000312103000063
Funding OrganizationThis 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.).
DepartmentNML分子-细胞生物力学与空间生命科学
Classification二类/Q2
Citation statistics
Cited Times:15[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/46602
Collection国家微重力实验室
Corresponding AuthorLong, M; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China.
Recommended Citation
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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