期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 411, 期 1, 页码 27-35出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2011.04.058
关键词
MthK K+ channel; steric hindrance; electrostatics; constriction point; single-channel electrophysiology
资金
- U.S. Department of Energy [DE-AC02-06CH11357]
- Howard Hughes Medical Institute
- Welch Foundation [I-1578]
- David and Lucile Packard Foundation
- Chinese Academy of Sciences Foundation of China [2320103112110201, SIMM1004KF-09]
- National Science and Technology Major Project [1G2009ZX09301-00101]
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.
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