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
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Allosteric Regulation
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Binding Sites
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Calcium / chemistry
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Calcium / metabolism*
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Cations, Divalent
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Cations, Monovalent
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Crystallography, X-Ray
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Humans
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Ion Channel Gating
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Ion Transport
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Lipid Bilayers / chemistry
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Membrane Potentials
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Models, Molecular
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Mutation
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Patch-Clamp Techniques
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Potassium / chemistry
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Potassium / metabolism*
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Potassium Channels, Calcium-Activated / chemistry*
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Potassium Channels, Calcium-Activated / genetics
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Potassium Channels, Calcium-Activated / metabolism
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
Substances
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Cations, Divalent
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Cations, Monovalent
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Lipid Bilayers
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Potassium Channels, Calcium-Activated
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Recombinant Fusion Proteins
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Potassium
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Calcium