title: Self-directed assembly and clustering of the cytoplasmic domains of inwardly rectifying Kir2.1 potassium channels on association with PSD-95.
abstract: The interaction of the extra-membranous domain of tetrameric inwardly rectifying Kir2.1 ion channels (Kir2.1NC(4)) with the membrane associated guanylate kinase protein PSD-95 has been studied using Transmission Electron Microscopy in negative stain. Three types of complexes were observed in electron micrographs corresponding to a 1:1 complex, a large self-enclosed tetrad complex and extended chains of linked channel domains. Using models derived from small angle X-ray scattering experiments in which high resolution structures from X-ray crystallographic and Nuclear Magnetic Resonance studies are positioned, the envelopes from single particle analysis can be resolved as a Kir2.1NC(4):PSD-95 complex and a tetrad of this unit (Kir2.1NC(4):PSD-95)(4). The tetrad complex shows the close association of the Kir2.1 cytoplasmic domains and the influence of PSD-95 mediated self-assembly on the clustering of these channels.
authors.affiliation: University of Manchester, Manchester Interdisciplinary Biocentre, Manchester M1 7DN, UK.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Fomina
authors.forename: Tina D
authors.initials: TD
authors.lastname: Howard
authors.forename: Olivia K
authors.initials: OK
authors.lastname: Sleator
authors.forename: Marina
authors.initials: M
authors.lastname: Golovanova
authors.forename: Liam
authors.initials: L
authors.lastname: O'Ryan
authors.forename: Mark L
authors.initials: ML
authors.lastname: Leyland
authors.forename: J Günter
authors.initials: JG
authors.lastname: Grossmann
authors.forename: Richard F
authors.initials: RF
authors.lastname: Collins
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Prince
mesh_terms: D003593:Cytoplasm / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015203:Reproducibility of Results; D012542:Scattering, Radiation
chemical_list: C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; C489461:Kir2.1 channel; D008565:Membrane Proteins; D024661:Potassium Channels, Inwardly Rectifying