title: Membrane insertion and topology of the amino-terminal domain TMD0 of multidrug-resistance associated protein 6 (MRP6).
abstract: The function of the ATP-binding cassette transporter MRP6 is unknown but mutations in its gene cause pseudoxanthoma elasticum. We have investigated the membrane topology of the N-terminal transmembrane domain TMD0 of MRP6 and the membrane integration and orientation propensities of its transmembrane segments (TMs) by glycosylation mapping. Results demonstrate that TMD0 has five TMs, an Nout-Cin topology and that the less hydrophobic TMs have strong preference for their orientation in the membrane that affects the neighboring TMs. Two disease-causing mutations changing the number of positive charges in the loops of TMD0 did not affect the membrane insertion efficiencies of the adjacent TMs.
authors.affiliation: Department of Sciences, University of Basilicata, 85100 Potenza, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Cuviello
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Tellgren-Roth
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lara
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Ruud Selin
authors.affiliation: Department of Sciences, University of Basilicata, 85100 Potenza, Italy.
authors.forename: Magnus
authors.initials: M
authors.lastname: Monné
authors.affiliation: Department of Sciences, University of Basilicata, 85100 Potenza, Italy.
authors.forename: Faustino
authors.initials: F
authors.lastname: Bisaccia
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden. Electronic address: ingmarie@dbb.su.se.
authors.forename: IngMarie
authors.initials: I
authors.lastname: Nilsson
authors.affiliation: Department of Sciences, University of Basilicata, 85100 Potenza, Italy. Electronic address: angela.ostuni@unibas.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Ostuni
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017384:Sequence Deletion
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human
keywords: ABCC6; ATP-binding cassette transporter; Membrane protein insertion; Multidrug-resistance associated protein 6; Pseudoxanthoma elasticum; Transmembrane domain