title: Molecular basis for K(ATP) assembly: transmembrane interactions mediate association of a K+ channel with an ABC transporter.
abstract: K(ATP) channels are large heteromultimeric complexes containing four subunits from the inwardly rectifying K+ channel family (Kir6.2) and four regulatory sulphonylurea receptor subunits from the ATP-binding cassette (ABC) transporter family (SUR1 and SUR2A/B). The molecular basis for interactions between these two unrelated protein families is poorly understood. Using novel trafficking-based interaction assays, coimmunoprecipitation, and current measurements, we show that the first transmembrane segment (M1) and the N terminus of Kir6.2 are involved in K(ATP) assembly and gating. Additionally, the transmembrane domains, but not the nucleotide-binding domains, of SUR1 are required for interaction with Kir6.2. The identification of specific transmembrane interactions involved in K(ATP) assembly may provide a clue as to how ABC proteins that transport hydrophobic substrates evolved to regulate other membrane proteins.
authors.affiliation: Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
authors.forename: B
authors.initials: B
authors.lastname: Schwappach
authors.forename: N
authors.initials: N
authors.lastname: Zerangue
authors.forename: Y N
authors.initials: YN
authors.lastname: Jan
authors.forename: L Y
authors.initials: LY
authors.lastname: Jan
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D014981:Xenopus
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D006023:Glycoproteins; D008565:Membrane Proteins; D015221:Potassium Channels