| 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.
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| Source Publication | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 2012-12-01 | |
| Volume | 287Issue:50Pages:42278-42287 |
| ISSN | 0021-9258 |
| Abstract | 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. |
| Keyword | Rectifier K++ Channels Beta-gamma-subunits Potassium Channels Crystal-structure G-proteins Structural Basis Voltage-sensor Pip2 Activation Dynamics |
| Subject Area | 生物力学 |
| URL | 查看原文 |
| Indexed By | SCI ; EI |
| Language | 英语 |
| WOS ID | WOS:000312103000063 |
| Funding Organization | 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.). |
| Department | NML分子-细胞生物力学与空间生命科学 |
| Classification | 二类/Q2 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/46602 |
| Collection | 微重力重点实验室 |
| Corresponding Author | Long, 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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