title: A structural motif for the voltage-gated potassium channel pore.
abstract: Mutation studies have identified a region of the S5-S6 loop of voltage-gated K+ channels (P region) responsible for teraethylammonium (TEA) block and permeation/selectivity properties. We previously modeled a similar region of the Na+ channel as four beta-hairpins with the C strands from each of the domains forming the external vestibule and with charged residues at the beta-turns forming the selectivity filter. However, the K+ channel P region amino acid composition is much more hydrophobic in this area. Here we propose a structural motif for the K+ channel pore based on the following postulates (Kv2.1 numbering). (i) The external TEA binding site is formed by four Tyr-380 residues; P loop residues participating in the internal TEA binding site are four Met-371 and Thr-372 residues. (ii) P regions form extended hairpins with beta-turns in sequence ITMT. (iii) only C ends of hairpins form the inner walls of the pore. (iv) They are extended nonregular strands with backbone carbonyl oxygens of segment VGYGD facing the pore with the conformation BRLRL. (v) Juxtaposition of P loops of the four subunits forms the pore. Fitting the external and internal TEA sites to TEA molecules predicts an hourglass-like pore with the narrowest point (GYG) as wide as 5.5 A, suggesting that selectivity may be achieved by interactions of carbonyls with partially hydrated K+. Other potential cation binding sites also exist in the pore.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Lipkind
authors.forename: D A
authors.initials: DA
authors.lastname: Hanck
authors.forename: H A
authors.initials: HA
authors.lastname: Fozzard
mesh_terms: D000595:Amino Acid Sequence; D051668:Delayed Rectifier Potassium Channels; D015640:Ion Channel Gating; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000502:physiology*; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D051669:Shab Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D051668:Delayed Rectifier Potassium Channels; D046911:Macromolecular Substances; D010455:Peptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; C076413:Shaker B potassium channel polypeptide; D051637:Shaker Superfamily of Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium