title: Editing of human K(V)1.1 channel mRNAs disrupts binding of the N-terminus tip at the intracellular cavity.
abstract: In the nervous system, A→I RNA editing has an important role in regulating neuronal excitability. Ligand-gated membrane receptors, synaptic proteins, as well as ion channels, are targets for recoding by RNA editing. Although scores of editing sites have been identified in the mammalian brain, little is known about the functional alterations that they cause, and even less about the mechanistic underpinnings of how they change protein function. We have previously shown that an RNA editing event (I,400 V) alters the inner permeation pathway of human K(V)1.1, modifying the kinetics of fast inactivation. Here we show that the channel's inactivation gate enters deep into the ion permeation pathway and the very tip establishes a direct hydrophobic interaction with the edited position. By converting I to V, the intimacy of the interaction is reduced, allowing the inactivation gate to unbind with much faster kinetics.
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de Valparaiso, Valparaiso V 2340000, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Angelica
authors.initials: A
authors.lastname: Lopez-Rodriguez
authors.forename: Deepa
authors.initials: D
authors.lastname: Srikumar
authors.forename: Joshua J C
authors.initials: JJ
authors.lastname: Rosenthal
authors.forename: Miguel
authors.initials: M
authors.lastname: Holmgren
mesh_terms: D002460:Cell Line; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D007700:Kinetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017393:RNA Editing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D051637:Shaker Superfamily of Potassium Channels