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: Vasundara Srinivasan, Antonio J Pierik, Roland Lill
• Journal: Science (New York, N.Y.) (Science) Vol. 343 Issue 6175 Pg. 1137-40 (Mar 07 2014) ISSN: 1095-9203 [Electronic] United States
• PMID: 24604199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATM1 protein, S cerevisiae
• ATP-Binding Cassette Transporters
• Saccharomyces cerevisiae Proteins
• Adenosine Triphosphate
• Glutathione

Topics

• ATP-Binding Cassette Transporters (chemistry)
• Adenosine Triphosphate (chemistry)
• Binding Sites
• Crystallography, X-Ray
• Glutathione (chemistry)
• Mitochondria (metabolism)
• Protein Multimerization
• Protein Stability
• Protein Structure, Secondary
• Saccharomyces cerevisiae Proteins (chemistry)