title: Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel.
abstract: High-conductance voltage- and Ca(2+)-activated K(+) channels function in many physiological processes that link cell membrane voltage and intracellular Ca(2+) concentration, including neuronal electrical activity, skeletal and smooth muscle contraction, and hair cell tuning. Like other voltage-dependent K(+) channels, Ca(2+)-activated K(+) channels open when the cell membrane depolarizes, but in contrast to other voltage-dependent K(+) channels, they also open when intracellular Ca(2+) concentrations rise. Channel opening by Ca(2+) is made possible by a structure called the gating ring, which is located in the cytoplasm. Recent structural studies have defined the Ca(2+)-free, closed, conformation of the gating ring, but the Ca(2+)-bound, open, conformation is not yet known. Here we present the Ca(2+)-bound conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca(2+), opens like the petals of a flower. The degree to which it opens explains how Ca(2+) binding can open the transmembrane pore. These findings present a molecular basis for Ca(2+) activation of K(+) channels and suggest new possibilities for targeting the gating ring to treat conditions such as asthma and hypertension.
authors.affiliation: Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Leonetti
authors.forename: Yichun
authors.initials: Y
authors.lastname: Hsiung
authors.forename: Roderick
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D004553:Electric Conductivity; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D018583:Pliability; D017434:Protein Structure, Tertiary; D015027:Zebrafish
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium