Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria

• Published in: Nature communications Vol. 13; no. 1; p. 4339
• Main Authors: Li, Ping, Hendricks, Amber L., Wang, Yong, Villones, Rhiza Lyne E., Lindkvist-Petersson, Karin, Meloni, Gabriele, Cowan, J. A., Wang, Kaituo, Gourdon, Pontus
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27-07-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 631/45/612/1237; 631/535/1258/1259; 631/57/2272/2273; 631/57/2283; 82/16; 82/58; 82/83; ATP-Binding Cassette Transporters - metabolism; Binding; Biologi; Biological Sciences; Clusters; Cofactors; Cryoelectron Microscopy; Electron microscopy; Eukaryotes; Exports; Glutathione; Homology; Humanities and Social Sciences; Humans; Iron; Iron - metabolism; Iron-sulfur proteins; Iron-Sulfur Proteins - metabolism; Maturation; Mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Molecular docking; Molecular Docking Simulation; multidisciplinary; Natural Sciences; Naturvetenskap; Proteins; Science; Science (multidisciplinary); Structural Biology; Strukturbiologi; Sulfur; Sulfur - metabolism; Sulfur proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32006-8

In eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these clusters are primarily biosynthesized in mitochondria. Previous studies suggest mitochondrial ABCB7-type exporters are involved in maturation of cytosolic iron-sulfur proteins. However, the molecular mechanism for how the ABCB7-type exporters participate in this process remains elusive. Here, we report a series of cryo-electron microscopy structures of a eukaryotic homolog of human ABCB7, CtAtm1, determined at average resolutions ranging from 2.8 to 3.2 Å, complemented by functional characterization and molecular docking in silico. We propose that CtAtm1 accepts delivery from glutathione-complexed iron-sulfur clusters. A partially occluded state links cargo-binding to residues at the mitochondrial matrix interface that line a positively charged cavity, while the binding region becomes internalized and is partially divided in an early occluded state. Collectively, our findings substantially increase the understanding of the transport mechanism of eukaryotic ABCB7-type proteins.
Mitochondrial Atm1 proteins play important roles in the maturation of certain cytosolic proteins. Here, the authors exploit cryo-EM to capture several structures of an Atm1. The findings shed new light on the molecular function of Atm1 transporters.