title: Specific mutations in mammalian P4-ATPase ATP8A2 catalytic subunit entail differential glycosylation of the accessory CDC50A subunit.
abstract: P4-ATPases, or flippases, translocate phospholipids between the two leaflets of eukaryotic biological membranes. They are essential to the physiologically crucial phospholipid asymmetry and involved in severe diseases, but their molecular structure and mechanism are still unresolved. Here, we show that in an extensive mutational alanine screening of the mammalian flippase ATP8A2 catalytic subunit, five mutations stand out by leading to reduced glycosylation of the accessory subunit CDC50A. These mutations may disturb the interaction between the subunits.
authors.affiliation: Department of Biomedicine, Aarhus University, Ole Worms Allé 4, Bldg. 1160, 8000 Aarhus C, Denmark; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: alv@sund.ku.dk.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Vestergaard
authors.affiliation: Department of Biomedicine, Aarhus University, Ole Worms Allé 4, Bldg. 1160, 8000 Aarhus C, Denmark.
authors.forename: Stine A
authors.initials: SA
authors.lastname: Mikkelsen
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre for Macular Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Coleman
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre for Macular Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada; Department of Ophthalmology and Visual Sciences, Centre for Macular Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Molday
authors.affiliation: Department of Biomedicine, Aarhus University, Ole Worms Allé 4, Bldg. 1160, 8000 Aarhus C, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Vilsen
authors.affiliation: Department of Biomedicine, Aarhus University, Ole Worms Allé 4, Bldg. 1160, 8000 Aarhus C, Denmark.
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Andersen
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain / Q000235:genetics*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D006031:Glycosylation; D008565:Membrane Proteins / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D049294:Phospholipid Transfer Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D021122:Protein Subunits
keywords: CDC50; Flippase; Interaction site; Membrane transport; P-type ATPase; TMEM30