title: Allosteric coupling of the inner activation gate to the outer pore of a potassium channel.
abstract: In potassium channels, functional coupling of the inner and outer pore gates may result from energetic interactions between residues and conformational rearrangements that occur along a structural path between them. Here, we show that conservative mutations of a residue near the inner activation gate of the Shaker potassium channel (I470) modify the rate of C-type inactivation at the outer pore, pointing to this residue as part of a pathway that couples inner gate opening to changes in outer pore structure and reduction of ion flow. Because they remain equally sensitive to rises in extracellular potassium, altered inactivation rates of the mutant channels are not secondary to modified binding of potassium to the outer pore. Conservative mutations of I470 also influence the interaction of the Shaker N-terminus with the inner gate, which separately affects the outer pore.
authors.affiliation: Department of Cellular and Physiological Sciences, Vancouver, British Columbia, V6T 1Z3.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Peters
authors.forename: David
authors.initials: D
authors.lastname: Fedida
authors.forename: Eric A
authors.initials: EA
authors.lastname: Accili
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000596:Amino Acids; D017124:Conserved Sequence; D005110:Extracellular Space / Q000378:metabolism; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009154:Mutation; D011188:Potassium / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D016415:Sequence Alignment; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D051637:Shaker Superfamily of Potassium Channels; D011188:Potassium