title: New roles for a key glycine and its neighboring residue in potassium channel gating.
abstract: Potassium channel activation regulates cellular excitability in cells such as neurons and heart. Ion channel activity relies on a switching mechanism between two conformations, the open and closed states, known as gating. It has been suggested that potassium channels are gated via a pivoted mechanism of the pore-lining helix. Our analysis suggests that hinging occurs at the residue immediately preceding the central glycine of the inner helix. Furthermore, we show that the highly conserved central glycine is necessary to prevent constraining interactions with critical residues in its vicinity, including those located in the selectivity filter. We show that such interactions can impair channel function, and that upon their removal channel activity can be restored.
authors.affiliation: Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Avia
authors.initials: A
authors.lastname: Rosenhouse-Dantsker
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics; D000818:Animals; D003198:Computer Simulation; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005998:Glycine / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D014981:Xenopus
chemical_list: D000596:Amino Acids; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D005998:Glycine