Crucial points within the pore as Determinants of K+ channel conductance and gating

Ning Shi, Weizhong Zeng, Sheng Ye, Yang Li, Youxing Jiang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalJournal of Molecular Biology
Volume411
Issue number1
DOIs
StatePublished - Aug 5 2011

Keywords

  • constriction point
  • electrostatics
  • single-channel electrophysiology
  • steric hindrance

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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