title: Structure of the MthK RCK in complex with cadmium.
abstract: RCK is a cytoplasmic regulatory domain of calcium-gated potassium channels. Binding of Ca(2+) by RCK leads to channel activation through a series of yet unknown conformational changes. Structures of the K(+) channel, MthK, and its cytoplasmic RCK domain revealed two binding sites for Ca(2+) per dimer. We determined the crystal structure of RCK in complex with Cd(2+) at 2.2A resolution. Cd(2+) activates MthK more efficiently, and binds at the same binding sites for Ca(2+) but with reduced coordination number. Two additional binding sites for Cd(2+) are found per dimer; one on the main Rossman-fold lobe, and the other on the small lobe of RCK. Using patch-clamp experiments, we demonstrate that Cd(2+) binding to these novel sites enhances activation by Cd(2+) and not by Ca(2+). The structure reveals a large negatively charged surface patch in the proximity of the Ca(2+)/Cd(2+) binding sites, charge neutralization of which appears to promote the channel open state.
authors.affiliation: Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Hay
authors.initials: H
authors.lastname: Dvir
authors.forename: Elvira
authors.initials: E
authors.lastname: Valera
authors.forename: Senyon
authors.initials: S
authors.lastname: Choe
mesh_terms: D001665:Binding Sites; D002104:Cadmium / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D024681:Potassium Channels, Calcium-Activated; D002104:Cadmium; D002118:Calcium