Work

Editing of human KV1.1 channel mRNAs disrupts binding of the N-terminus tip at the intracellular cavity

Year: 2011

Type: article

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 (I400 V) alters the inner permeation pathway of human KV1.1, 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. RNA editing is important in regulating neuronal excitability, and a specific editing event has been shown to alter the permeation pathway of voltage-gate potassium channels. Gonzalezet al.find that the tip of the channel's inactivation gate makes a direct hydrophobic interaction with the edited position.

Source: Nature Communications

DOI: 10.1038/ncomms1446

Authors: Carlos Gonzalez, Angelica Lopez-Rodriguez, Deepa Srikumar, Joshua J.C. Rosenthal, Miguel Holmgren

Institutions: University of Valparaíso, National Institutes of Health, National Institute of Neurological Disorders and Stroke, University of Puerto Rico, Medical Sciences Campus

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $6,990