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Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain
Frank J Smith1, Victor P T Pau, Gino Cingolani
1Department of Biochemistry, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, Pennsylvania 19140, USA.
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.
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