Crucial Points within the Pore as Determinants of K+ Channel Conductance and Gating
文献类型：期刊论文
| 作者 | Shi, Ning2,3; Zeng, Weizhong2,3; Ye, Sheng4; Li, Yang1 ; Jiang, Youxing2,3
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| 刊名 | JOURNAL OF MOLECULAR BIOLOGY
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| 出版日期 | 2011-08-05 |
| 卷号 | 411期号:1页码:27-35 |
| 关键词 | MthK K+ channel steric hindrance electrostatics constriction point single-channel electrophysiology |
| ISSN号 | 0022-2836 |
| DOI | 10.1016/j.jmb.2011.04.058 |
| 文献子类 | Article |
| 英文摘要 | While selective for K+, K+ channels vary significantly among their rate of ion permeation. Here, we probe the effect of steric hindrance and electrostatics within the ion conduction pathway on K+ permeation in the MthK K+ channel using structure-based mutagenesis combined with single-channel electrophysiology and X-ray crystallography. We demonstrate that changes in side-chain size and polarity at Ala88, which forms the constriction point of the open MthK pore, have profound effects on single-channel conductance as well as open probability. We also reveal that the negatively charged Glu92s at the intracellular entrance of the open pore form an electrostatic trap, which stabilizes a hydrated K+ and facilitates ion permeation. This electrostatic attraction is also responsible for intracellular divalent blockage, which renders the channel inward rectified in the presence of Ca2+. In light of the high structural conservation of the selectivity filter, the size and chemical environment differences within the portion of the ion conduction pathway other than the filter are likely the determinants for the conductance variations among K+ channels. (C) 2011 Elsevier Ltd. All rights reserved. |
| WOS关键词 | POTASSIUM CHANNEL ; CRYSTAL-STRUCTURE ; ATOMIC-STRUCTURE ; MTHK ; RESOLUTION ; RING ; SELECTIVITY ; MECHANISM ; INSIGHTS ; EPILEPSY |
| 资助项目 | U.S. Department of Energy[DE-AC02-06CH11357] ; Howard Hughes Medical Institute[00000000] ; Welch Foundation[I-1578] ; David and Lucile Packard Foundation[00000000] ; Chinese Academy of Sciences Foundation of China[2320103112110201] ; Chinese Academy of Sciences Foundation of China[SIMM1004KF-09] ; National Science and Technology Major Project[1G2009ZX09301-00101] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000293938300003 |
| 出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278446]  |
| 专题 | 药理学第一研究室 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 药理学第二研究室 |
| 通讯作者 | Li, Yang |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA; 3.Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA; 4.Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shi, Ning,Zeng, Weizhong,Ye, Sheng,et al. Crucial Points within the Pore as Determinants of K+ Channel Conductance and Gating[J]. JOURNAL OF MOLECULAR BIOLOGY,2011,411(1):27-35. |
| APA | Shi, Ning,Zeng, Weizhong,Ye, Sheng,Li, Yang,&Jiang, Youxing.(2011).Crucial Points within the Pore as Determinants of K+ Channel Conductance and Gating.JOURNAL OF MOLECULAR BIOLOGY,411(1),27-35. |
| MLA | Shi, Ning,et al."Crucial Points within the Pore as Determinants of K+ Channel Conductance and Gating".JOURNAL OF MOLECULAR BIOLOGY 411.1(2011):27-35. |
入库方式： OAI收割
来源：上海药物研究所
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