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

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.