Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, 35032 Marburg, Germany.
Science. 2014 Mar 7;343(6175):1137-40. 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.
酵母线粒体 ABC 转运蛋白 Atm1 与谷胱甘肽协同作用，负责将细胞质-核铁硫蛋白生物发生和细胞铁调节所需的底物输出。人类同源物 ABCB7 的缺陷导致 X 连锁铁粒幼细胞贫血 XLSA/A。在这里，我们分别以 3.06 和 3.38 埃的分辨率报道了自由态和谷胱甘肽结合态 Atm1 的向内开放构象的晶体结构。谷胱甘肽结合位点包含 XLSA/A 中突变的残基，位于靠近内膜表面的大腔中。两个无核苷酸的腺苷 5'-三磷酸结合结构域虽然没有相互作用，但通过 Atm1 二聚体的两个 C 末端α螺旋的紧密相互作用保持在近距离。由此产生的蛋白质稳定性可能是所有 ABC 外排泵的共同结构特征。
