title: 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.
authors.affiliation: Department of Biochemistry, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Smith
authors.forename: Victor P T
authors.initials: VP
authors.lastname: Pau
authors.forename: Gino
authors.initials: G
authors.lastname: Cingolani
authors.forename: Brad S
authors.initials: BS
authors.lastname: Rothberg
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002413:Cations, Divalent; D002414:Cations, Monovalent; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015640:Ion Channel Gating; D017136:Ion Transport; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials; D008958:Models, Molecular; D009154:Mutation; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000737:chemistry / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D002414:Cations, Monovalent; D008051:Lipid Bilayers; D024681:Potassium Channels, Calcium-Activated; D011993:Recombinant Fusion Proteins; D011188:Potassium; D002118:Calcium