title: Structural Titration of Slo2.2, a Na+-Dependent K+Channel.
abstract: The stable structural conformations that occur along the complete reaction coordinate for ion channel opening have never been observed. In this study, we describe the equilibrium ensemble of structures of Slo2.2, a neuronal Na+-activated K+channel, as a function of the Na+concentration. We find that Slo2.2 exists in multiple closed conformations whose relative occupancies are independent of Na+concentration. An open conformation emerges from an ensemble of closed conformations in a highly Na+-dependent manner, without evidence of Na+-dependent intermediates. In other words, channel opening is a highly concerted, switch-like process. The midpoint of the structural titration matches that of the functional titration. A maximum open conformation probability approaching 1.0 and maximum functional open probability approaching 0.7 imply that, within the class of open channels, there is a subclass that is not permeable to ions.
authors.affiliation: Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 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, NY 10065, USA. Electronic address: mackinn@rockefeller.edu.
authors.forename: Roderick
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000737:chemistry* / Q000378:metabolism; D002645:Chickens / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D012964:Sodium / Q000737:chemistry
chemical_list: D030161:Avian Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D012964:Sodium
keywords: K(+) channel; Slo2 channel; channel gating mechanism; cryo-electron microscopy; high conductance K(+) channel; ion channel gating; ligand-gated ion channel; molecular structure