title: Cryo-electron microscopy structure of the Slo2.2 Na(+)-activated K(+) channel.
abstract: Na(+)-activated K(+) channels are members of the Slo family of large conductance K(+) channels that are widely expressed in the brain, where their opening regulates neuronal excitability. These channels fulfil a number of biological roles and have intriguing biophysical properties, including conductance levels that are ten times those of most other K(+) channels and gating sensitivity to intracellular Na(+). Here we present the structure of a complete Na(+)-activated K(+) channel, chicken Slo2.2, in the Na(+)-free state, determined by cryo-electron microscopy at a nominal resolution of 4.5 ångströms. The channel is composed of a large cytoplasmic gating ring, in which resides the Na(+)-binding site and a transmembrane domain that closely resembles voltage-gated K(+) channels. In the structure, the cytoplasmic domain adopts a closed conformation and the ion conduction pore is also closed. The structure reveals features that can explain the unusually high conductance of Slo channels and how contraction of the cytoplasmic gating ring closes the pore.
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: Peng
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Cell Biology and Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Li
authors.affiliation: Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Hsuing
authors.affiliation: Department of Cell Biology and Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
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; D001665:Binding Sites; D002645:Chickens; D020285:Cryoelectron Microscopy; D003593:Cytoplasm / Q000378:metabolism; D004553:Electric Conductivity; D015640:Ion Channel Gating; D017136:Ion Transport; D008958:Models, Molecular; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D017434:Protein Structure, Tertiary; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D015221:Potassium Channels; D012964:Sodium