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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / metabolism*
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Cell Line
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Cell Membrane / physiology
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Cell Membrane / ultrastructure
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Diacetyl / analogs & derivatives
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Diacetyl / pharmacology
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Dimerization
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Dithiothreitol / pharmacology
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Female
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Glycosylation
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Humans
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Macromolecular Substances
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Membrane Potentials / drug effects
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Molecular Sequence Data
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Myocardium / metabolism*
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Oocytes / physiology
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Potassium Channels / biosynthesis*
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Potassium Channels / chemistry*
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Potassium Channels / physiology
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Potassium Channels, Tandem Pore Domain*
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Protein Structure, Secondary
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Spodoptera
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Transfection
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Xenopus
Substances
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KCNK1 protein, human
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Macromolecular Substances
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Potassium Channels
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Potassium Channels, Tandem Pore Domain
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Recombinant Proteins
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diacetylmonoxime
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Diacetyl
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Dithiothreitol