Crystal Structures of Nucleotide-Free and Glutathione-Bound Mitochondrial ABC Transporter Atm1

• Published in: Science (American Association for the Advancement of Science) 2014-03, Vol.343 (6175), p.1137-1140
• Main Authors: Srinivasan, Vasundara, Pierik, Antonio J., Lill, Roland
• Format: Article
• Language: English
• Subjects: ABC transporters; Adenosine triphosphatase; Adenosine Triphosphate - chemistry; ATP binding cassette transporters; ATP-Binding Cassette Transporters - chemistry; Bacteria; Binding Sites; Crystal structure; Crystallography, X-Ray; Crystals; Dimers; Electron density; Glutathione - chemistry; Mitochondria; Mitochondria - metabolism; Molecules; Monomers; Protein Multimerization; Protein Stability; Protein Structure, Secondary; Proteins; Saccharomyces cerevisiae Proteins - chemistry; Yeast; Yeasts
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1246729

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.