The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels
文献类型：期刊论文
| 作者 | 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
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2012-12-01 |
| 卷号 | 287期号:50页码:42278-42287 |
| 通讯作者邮箱 | mlong@imech.ac.cn;z.hailin@yahoo.com; delogothetis@vcu.edu |
| 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 |
| 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 |
| 通讯作者 | Long, M ; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, 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 |
| 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. |
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来源：力学研究所
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