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Title:
The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels
Author: An HL; Lv SQ(吕守芹); Li JW; Meng XY; Zhan Y; Cui M; Long M(龙勉); Zhang HL; Logothetis DE
Source: JOURNAL OF BIOLOGICAL CHEMISTRY
Issued Date: 2012-12-01
Volume: 287, Issue:50, Pages:42278-42287
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
Language: 英语
Indexed Type: SCI ; EI
Corresponding Author: Long, M ; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China.
Correspondent Email: mlong@imech.ac.cn;z.hailin@yahoo.com; delogothetis@vcu.edu
Related URLs: 查看原文
WOS ID: WOS:000312103000063
ISSN: 0021-9258
Rank: [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
Subject: 交叉与边缘领域的力学::生物力学
Department: NML分子-细胞生物力学与空间生命科学
Classification: 二类/Q2
Citation statistics:
Content Type: 期刊论文
URI: http://dspace.imech.ac.cn/handle/311007/46602
Appears in Collections:国家微重力实验室_期刊论文

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Recommended Citation:
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,2012-12-01,287(50):42278-42287.
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