Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1.

TitleCrystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1.
Publication TypeJournal Article
Year of Publication2014
AuthorsSrinivasan, V, Pierik, AJ, Lill, R
JournalScience
Volume343
Issue6175
Pagination1137-40
Date Published2014 Mar 7
ISSN1095-9203
KeywordsAdenosine Triphosphate, ATP-Binding Cassette Transporters, Binding Sites, Crystallography, X-Ray, Glutathione, Mitochondria, Protein Multimerization, Protein Stability, Protein Structure, Secondary, Saccharomyces cerevisiae Proteins
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.

DOI10.1126/science.1246729
Alternate JournalScience
Citation Key10.1126/science.1246729
PubMed ID24604199