Structural mechanism of C-type inactivation in K(+) channels

Nature. 2010 Jul 8;466(7303):203-8. doi: 10.1038/nature09153.

Abstract

Interconversion between conductive and non-conductive forms of the K(+) channel selectivity filter underlies a variety of gating events, from flicker transitions (at the microsecond timescale) to C-type inactivation (millisecond to second timescale). Here we report the crystal structure of the Streptomyces lividans K(+) channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were identified with openings ranging from 12 A in closed KcsA (Calpha-Calpha distances at Thr 112) to 32 A when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures indicate a molecular basis for C-type inactivation in K(+) channels.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Electrons
  • Ion Channel Gating*
  • Kinetics
  • Models, Biological
  • Models, Molecular
  • Potassium / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / metabolism
  • Protein Conformation
  • Streptomyces lividans / chemistry*
  • Structure-Activity Relationship

Substances

  • Bacterial Proteins
  • Potassium Channels
  • prokaryotic potassium channel
  • Potassium

Associated data

  • PDB/3BF5
  • PDB/3F5W
  • PDB/3F7V
  • PDB/3F7Y
  • PDB/3FB6