title: Ion selectivity in a semisynthetic K+ channel locked in the conductive conformation.
abstract: Potassium channels are K+-selective protein pores in cell membrane. The selectivity filter is the functional unit that allows K+ channels to distinguish potassium (K+) and sodium (Na+) ions. The filter's structure depends on whether K+ or Na+ ions are bound inside it. We synthesized a K+ channel containing the d-enantiomer of alanine in place of a conserved glycine and found by x-ray crystallography that its filter maintains the K+ (conductive) structure in the presence of Na+ and very low concentrations of K+. This channel conducts Na+ in the absence of K+ but not in the presence of K+. These findings demonstrate that the ability of the channel to adapt its structure differently to K+ and Na+ is a fundamental aspect of ion selectivity, as is the ability of multiple K+ ions to compete effectively with Na+ for the conductive filter.
authors.affiliation: Laboratories of Molecular Neurobiology and Biophysics and Synthetic Protein Chemistry, Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Francis I
authors.initials: FI
authors.lastname: Valiyaveetil
authors.forename: Manuel
authors.initials: M
authors.lastname: Leonetti
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
authors.forename: Roderick
authors.initials: R
authors.lastname: Mackinnon
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004594:Electrophysiology; D008051:Lipid Bilayers; D008081:Liposomes; D008958:Models, Molecular; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D015221:Potassium Channels; D011188:Potassium