Mechanism for selectivity-inactivation coupling in KcsA potassium channels Academic Article uri icon

Overview

MeSH Major

  • Bacterial Proteins
  • Ion Channel Gating
  • Potassium Channels
  • Protein Conformation

abstract

  • Structures of the prokaryotic K(+) channel, KcsA, highlight the role of the selectivity filter carbonyls from the GYG signature sequence in determining a highly selective pore, but channels displaying this sequence vary widely in their cation selectivity. Furthermore, variable selectivity can be found within the same channel during a process called C-type inactivation. We investigated the mechanism for changes in selectivity associated with inactivation in a model K(+) channel, KcsA. We found that E71A, a noninactivating KcsA mutant in which a hydrogen-bond behind the selectivity filter is disrupted, also displays decreased K(+) selectivity. In E71A channels, Na(+) permeates at higher rates as seen with and flux measurements and analysis of intracellular Na(+) block. Crystal structures of E71A reveal that the selectivity filter no longer assumes the "collapsed," presumed inactivated, conformation in low K(+), but a "flipped" conformation, that is also observed in high K(+), high Na(+), and even Na(+) only conditions. The data reveal the importance of the E71-D80 interaction in both favoring inactivation and maintaining high K(+) selectivity. We propose a molecular mechanism by which inactivation and K(+) selectivity are linked, a mechanism that may also be at work in other channels containing the canonical GYG signature sequence.

publication date

  • March 29, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3069191

Digital Object Identifier (DOI)

  • 10.1073/pnas.1014186108

PubMed ID

  • 21402935

Additional Document Info

start page

  • 5272

end page

  • 7

volume

  • 108

number

  • 13