Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation
文献类型：期刊论文
| 作者 | Chen, Liping1,2; Zhang, Qiansen1,2; Qiu, Yunguang1,2; Li, Zanyuan1,2; Chen, Zhuxi1,2; Jiang, Hualiang1,2 ; Li, Yang1,2; Yang, Huaiyu1,2
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| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 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. |
| 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 |
| 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研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000362813700001 |
| 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). |
入库方式： OAI收割
来源：上海药物研究所
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