title: Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1.
abstract: The yeast mitochondrial ABC transporter Atm1, in concert with glutathione, functions in the export of a substrate required for cytosolic-nuclear iron-sulfur protein biogenesis and cellular iron regulation. Defects in the human ortholog ABCB7 cause the sideroblastic anemia XLSA/A. Here, we report the crystal structures of free and glutathione-bound Atm1 in inward-facing, open conformations at 3.06- and 3.38-angstrom resolution, respectively. The glutathione binding site includes a residue mutated in XLSA/A and is located close to the inner membrane surface in a large cavity. The two nucleotide-free adenosine 5'-triphosphate binding domains do not interact yet are kept in close vicinity through tight interaction of the two C-terminal α-helices of the Atm1 dimer. The resulting protein stabilization may be a common structural feature of all ABC exporters.
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, 35032 Marburg, Germany.
authors.forename: Vasundara
authors.initials: V
authors.lastname: Srinivasan
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pierik
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005978:Glutathione / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism*; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*
chemical_list: C091561:ATM1 protein, S cerevisiae; D018528:ATP-Binding Cassette Transporters; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D005978:Glutathione