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Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating

文献类型：期刊论文

作者Zhang, Qiansen3; Zhou, Pingzheng1; Chen, Zhuxi3; Li, Min1,2,4; Jiang, Hualiang3; Gao, Zhaobing1; Yang, Huaiyu3
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2013-12-10
卷号110期号:50页码:20093-20098
关键词lipid membrane membrane protein M current
ISSN号0027-8424
DOI10.1073/pnas.1312483110
文献子类Article
英文摘要The S4 segment and the S4-S5 linker of voltage-gated potassium (Kv) channels are crucial for voltage sensing. Previous studies on the Shaker and Kv1.2 channels have shown that phosphatidylinositol-4,5-bisphosphate (PIP2) exerts opposing effects on Kv channels, upregulating the current amplitude, while decreasing the voltage sensitivity. Interactions between PIP2 and the S4 segment or the S4-S5 linker in the closed state have been highlighted to explain the effects of PIP2 on voltage sensitivity. Here, we show that PIP2 preferentially interacts with the S4-S5 linker in the open-state KCNQ2 (Kv7.2) channel, whereas it contacts the S2-S3 loop in the closed state. These interactions are different from the PIP2-Shaker and PIP2-Kv1.2 interactions. Consistently, PIP2 exerts different effects on KCNQ2 relative to the Shaker and Kv1.2 channels; PIP2 up-regulates both the current amplitude and voltage sensitivity of the KCNQ2 channel. Disruption of the interaction of PIP2 with the S4-S5 linker by a single mutation decreases the voltage sensitivity and current amplitude, whereas disruption of the interaction with the S2-S3 loop does not alter voltage sensitivity. These results provide insight into the mechanism of PIP2 action on KCNQ channels. In the closed state, PIP2 is anchored at the S2-S3 loop; upon channel activation, PIP2 interacts with the S4-S5 linker and is involved in channel gating.
WOS关键词RECEPTOR-MEDIATED INHIBITION ; GATED POTASSIUM CHANNELS ; RECTIFIER K+ CHANNELS ; FULL-LENGTH KCSA ; MOLECULAR-DYNAMICS ; CRYSTAL-STRUCTURE ; MEMBRANE PHOSPHOINOSITIDES ; ION CHANNELS ; PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE ; 4,5-BISPHOSPHATE
资助项目State Key Program of Basic Research of China[2013CB910604] ; State Key Program of Basic Research of China[2009CB918502] ; National Natural Science Foundation of China[81173027] ; National Natural Science Foundation of China[81072579] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21210003] ; National Institutes of Health[U54 MH084691] ; Shanghai Science and Technology Development Funds[12QA1404000] ; Shanghai Science and Technology Development Funds[13JC1406700] ; Special Research Foundation of Chinese Academy of Sciences[61327014] ; Hi-Tech Research and Development Program of China[2012AA020302] ; Hi-Tech Research and Development Program of China[2012AA01A305] ; SA-SIBS Scholarship Program[00000000]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000328061700041
出版者NATL ACAD SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/277337]  
专题神经药理学研究国际科学家工作站
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药物发现与设计中心
通讯作者Yang, Huaiyu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Chinese Acad Sci Key Lab Receptor Res, Shanghai 201203, Peoples R China;
2.Johns Hopkins Univ, Sch Med, Johns Hopkins Ion Channel Ctr, Baltimore, MD 21205 USA
3.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
4.Johns Hopkins Univ, High Throughput Biol Ctr, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA;
推荐引用方式
GB/T 7714		 Zhang, Qiansen,Zhou, Pingzheng,Chen, Zhuxi,et al. Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2013,110(50):20093-20098.
APA Zhang, Qiansen.,Zhou, Pingzheng.,Chen, Zhuxi.,Li, Min.,Jiang, Hualiang.,...&Yang, Huaiyu.(2013).Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,110(50),20093-20098.
MLA Zhang, Qiansen,et al."Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110.50(2013):20093-20098.

入库方式： OAI收割

来源：上海药物研究所

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