title: Conserved gating hinge in ligand- and voltage-dependent K+ channels.
abstract: Ion channels open and close their pore in a process called gating. On the basis of crystal structures of two voltage-independent K(+) channels, KcsA and MthK, a conformational change for gating has been proposed whereby the inner helix bends at a glycine hinge point (gating hinge) to open the pore and straightens to close it. Here we ask if a similar gating hinge conformational change underlies the mechanics of pore opening of two eukaryotic voltage-dependent K(+) channels, Shaker and BK channels. In the Shaker channel, substitution of the gating hinge glycine with alanine and several other amino acids prevents pore opening, but the ability to open is recovered if a secondary glycine is introduced at an adjacent position. A proline at the gating hinge favors the open state of the Shaker channel as if by preventing inner helix straightening. In BK channels, which have two adjacent glycine residues, opening is significantly hindered in a graded manner with single and double mutations to alanine. These results suggest that K(+) channels, whether ligand- or voltage-dependent, open when the inner helix bends at a conserved glycine gating hinge.
authors.affiliation: Department of Life Sciences and Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
authors.forename: Elhanan
authors.initials: E
authors.lastname: Magidovich
authors.forename: Ofer
authors.initials: O
authors.lastname: Yifrach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D017124:Conserved Sequence / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000737:chemistry / Q000235:genetics; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008024:Ligands; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D051637:Shaker Superfamily of Potassium Channels; D014982:Xenopus laevis
chemical_list: D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008024:Ligands; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels; D005998:Glycine