title: Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.
abstract: TWIK-1 is a new type of K+ channel with two P domains and is abundantly expressed in human heart and brain. Here we show that TWIK-1 subunits can self-associate to give dimers containing an interchain disulfide bridge. This assembly involves a 34 amino acid domain that is localized to the extracellular M1P1 linker loop. Cysteine 69 which is part of this interacting domain is implicated in the formation of the disulfide bond. Replacing this cysteine with a serine residue results in the loss of functional K+ channel expression. This is the first example of a covalent association of functional subunits in voltage-sensitive channels via a disulfide bridge.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660, Valbonne, France.
authors.forename: F
authors.initials: F
authors.lastname: Lesage
authors.forename: R
authors.initials: R
authors.lastname: Reyes
authors.forename: M
authors.initials: M
authors.lastname: Fink
authors.forename: F
authors.initials: F
authors.lastname: Duprat
authors.forename: E
authors.initials: E
authors.lastname: Guillemare
authors.forename: M
authors.initials: M
authors.lastname: Lazdunski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D019281:Dimerization; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D006031:Glycosylation; D006801:Humans; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D015221:Potassium Channels / Q000096:biosynthesis* / Q000737:chemistry* / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018411:Spodoptera; D014162:Transfection; D014981:Xenopus
chemical_list: C109137:KCNK1 protein, human; D046911:Macromolecular Substances; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins; C004717:diacetylmonoxime; D003931:Diacetyl; D004229:Dithiothreitol