Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation

doi:10.1038/srep15079

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation
	Chen, Liping 1,2; Zhang, Qiansen 1,2; Qiu, Yunguang 1,2; Li, Zanyuan 1,2; Chen, Zhuxi 1,2; Jiang, Hualiang1,2 ; Li, Yang1,2 ; Yang, Huaiyu 1,2
刊名	SCIENTIFIC REPORTS
	2015-10-15
卷号	5
ISSN号	2045-2322
DOI	10.1038/srep15079
文献子类	Article
英文摘要	Published studies of lipid-protein interactions have mainly focused on lipid binding to an individual site of the protein. Here, we show that a lipid can migrate between different binding sites in a protein and this migration modulates protein function. Voltage-gated potassium (Kv) channels have several potential binding sites for phosphatidylinositol-4,5-bisphosphate (PIP2). Our molecular dynamics (MD) simulations on the KCNQ2 channel reveal that PIP2 preferentially binds to the S4-S5 linker when the channel is in the open state while maintains a certain probability of migrating to the S2-S3 linker. Guided by the MD results, electrophysiological experiments using KCNQ2, KCNQ1, and hERG channels show that the migration of PIP2 toward the S2-S3 linker controls the deactivation rate of the channel. The data suggest that PIP2 can migrate between different binding sites in Kv channels with significant impacts on channel deactivation, casting new insights into the dynamics and physiological functions of lipid-protein interactions.
资助项目	Ministry of Science and Technology of China[2013CB910601] ; Ministry of Science and Technology of China[2013CB910604] ; National Natural Science Foundation of China[21422208] ; National Natural Science Foundation of China[81173027] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[3117101101] ; National Natural Science Foundation of China[91413122] ; National Natural Science Foundation of China[31128009] ; SA-SIBS Scholarship Program[00000000]
WOS关键词	DEPENDENT K+ CHANNEL ; RECEPTOR-MEDIATED INHIBITION ; FULL-LENGTH KCSA ; ION CHANNELS ; CRYSTAL-STRUCTURE ; INWARD RECTIFIER ; KCNQ CHANNELS ; GATING CHARGE ; S4-S5 LINKER ; CARDIAC-ARRHYTHMIA
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000362813700001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276362]
专题	药理学第二研究室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
通讯作者	Li, Yang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Liping,Zhang, Qiansen,Qiu, Yunguang,et al. Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation[J]. SCIENTIFIC REPORTS,2015,5.
APA	Chen, Liping.,Zhang, Qiansen.,Qiu, Yunguang.,Li, Zanyuan.,Chen, Zhuxi.,...&Yang, Huaiyu.(2015).Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation.SCIENTIFIC REPORTS,5.
MLA	Chen, Liping,et al."Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation".SCIENTIFIC REPORTS 5(2015).