title: KCNKØ: opening and closing the 2-P-domain potassium leak channel entails "C-type" gating of the outer pore.
abstract: Essential to nerve and muscle function, little is known about how potassium leak channels operate. KCNKØ opens and closes in a kinase-dependent fashion. Here, the transition is shown to correspond to changes in the outer aspect of the ion conduction pore. Voltage-gated potassium (VGK) channels open and close via an internal gate; however, they also have an outer pore gate that produces "C-type" inactivation. While KCNKØ does not inactivate, KCNKØ and VGK channels respond in like manner to outer pore blockers, potassium, mutations, and chemical modifiers. Structural relatedness is confirmed: VGK residues that come close during C-type gating predict KCNKØ sites that crosslink (after mutation to cysteine) to yield channels controlled by reduction and oxidization. We conclude that similar outer pore gates mediate KCNKØ opening and closing and VGK channel C-type inactivation despite their divergent structures and physiological roles.
authors.affiliation: Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zilberberg
authors.forename: N
authors.initials: N
authors.lastname: Ilan
authors.forename: S A
authors.initials: SA
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D017353:Gene Deletion; D006639:Histidine / Q000235:genetics; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D016296:Mutagenesis / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D011188:Potassium / Q000493:pharmacokinetics; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels; D006639:Histidine; D019789:Tetraethylammonium; D015032:Zinc; D011188:Potassium