Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain

Nat Commun. 2013;4:2621. doi: 10.1038/ncomms3621.

Abstract

Ligand binding sites within proteins can interact by allosteric mechanisms to modulate binding affinities and control protein function. Here we present crystal structures of the regulator of K+ conductance (RCK) domain from a K+ channel, MthK, which reveal the structural basis of allosteric coupling between two Ca2+ regulatory sites within the domain. Comparison of RCK domain crystal structures in a range of conformations and with different numbers of regulatory Ca2+ ions bound, combined with complementary electrophysiological analysis of channel gating, suggests chemical interactions that are important for modulation of ligand binding and subsequent channel opening.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Allosteric Regulation
  • Binding Sites
  • Calcium / chemistry
  • Calcium / metabolism*
  • Cations, Divalent
  • Cations, Monovalent
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Humans
  • Ion Channel Gating
  • Ion Transport
  • Lipid Bilayers / chemistry
  • Membrane Potentials
  • Models, Molecular
  • Mutation
  • Patch-Clamp Techniques
  • Potassium / chemistry
  • Potassium / metabolism*
  • Potassium Channels, Calcium-Activated / chemistry*
  • Potassium Channels, Calcium-Activated / genetics
  • Potassium Channels, Calcium-Activated / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Cations, Divalent
  • Cations, Monovalent
  • Lipid Bilayers
  • Potassium Channels, Calcium-Activated
  • Recombinant Fusion Proteins
  • Potassium
  • Calcium