|Title||Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Srinivasan, V, Pierik, AJ, Lill, R|
|Date Published||2014 Mar 7|
|Keywords||Adenosine Triphosphate, ATP-Binding Cassette Transporters, Binding Sites, Crystallography, X-Ray, Glutathione, Mitochondria, Protein Multimerization, Protein Stability, Protein Structure, Secondary, Saccharomyces cerevisiae Proteins|
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.