title: Structural basis for gating the high-conductance Ca2+-activated K+channel.
abstract: The precise control of an ion channel gate by environmental stimuli is crucial for the fulfilment of its biological role. The gate in Slo1 K+channels is regulated by two separate stimuli, intracellular Ca2+concentration and membrane voltage. Slo1 is thus central to understanding the relationship between intracellular Ca2+and membrane excitability. Here we present the Slo1 structure from Aplysia californica in the absence of Ca2+and compare it with the Ca2+-bound channel. We show that Ca2+binding at two unique binding sites per subunit stabilizes an expanded conformation of the Ca2+sensor gating ring. These conformational changes are propagated from the gating ring to the pore through covalent linkers and through protein interfaces formed between the gating ring and the voltage sensors. The gating ring and the voltage sensors are directly connected through these interfaces, which allow membrane voltage to regulate gating of the pore by influencing the Ca2+sensors.
authors.affiliation: Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Hite
authors.affiliation: Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tao
authors.affiliation: Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Roderick
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D000818:Animals; D001048:Aplysia / Q000737:chemistry*; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000494:pharmacology; D020285:Cryoelectron Microscopy; D004492:Edetic Acid / Q000737:chemistry / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D008274:Magnesium / Q000494:pharmacology; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D021122:Protein Subunits; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium