title: Modulation of potassium channel function by methionine oxidation and reduction.
abstract: Oxidation of amino acid residues in proteins can be caused by a variety of oxidizing agents normally produced by cells. The oxidation of methionine in proteins to methionine sulfoxide is implicated in aging as well as in pathological conditions, and it is a reversible reaction mediated by a ubiquitous enzyme, peptide methionine sulfoxide reductase. The reversibility of methionine oxidation suggests that it could act as a cellular regulatory mechanism although no such in vivo activity has been demonstrated. We show here that oxidation of a methionine residue in a voltage-dependent potassium channel modulates its inactivation. When this methionine residue is oxidized to methionine sulfoxide, the inactivation is disrupted, and it is reversed by coexpression with peptide methionine sulfoxide reductase. The results suggest that oxidation and reduction of methionine could play a dynamic role in the cellular signal transduction process in a variety of systems.
authors.affiliation: Department of Physiology and Biophysics, Bowen 5660, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Ciorba
authors.forename: S H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: H
authors.initials: H
authors.lastname: Weissbach
authors.forename: N
authors.initials: N
authors.lastname: Brot
authors.forename: T
authors.initials: T
authors.lastname: Hoshi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015640:Ion Channel Gating; D008715:Methionine / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D014981:Xenopus
chemical_list: D015221:Potassium Channels; D008715:Methionine