1. Anamorsin Is a [2Fe-2S] Cluster-Containing Substrate of the Mia40-Dependent Mitochondrial Protein Trapping Machinery
- Author
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Ivano Bertini, Francesca Boscaro, Julia Winkelmann, Lucia Banci, Maciej Mikolajczyk, Afroditi Chatzi, Kostas Tokatlidis, and Simone Ciofi-Baffoni
- Subjects
Iron-Sulfur Proteins ,Saccharomyces cerevisiae Proteins ,Mitochondrial intermembrane space ,Stereochemistry ,Iron ,Clinical Biochemistry ,Saccharomyces cerevisiae ,Mitochondrion ,Biology ,010402 general chemistry ,Mitochondrial Membrane Transport Proteins ,01 natural sciences ,Biochemistry ,Substrate Specificity ,03 medical and health sciences ,Oxidoreductase ,Mitochondrial Precursor Protein Import Complex Proteins ,Drug Discovery ,Humans ,Cysteine ,Mitochondrial protein ,Molecular Biology ,030304 developmental biology ,chemistry.chemical_classification ,Pharmacology ,0303 health sciences ,Intracellular Signaling Peptides and Proteins ,General Medicine ,Mitochondria ,Protein Structure, Tertiary ,0104 chemical sciences ,Cytosol ,chemistry ,Molecular Medicine ,Oxidation-Reduction ,Linker ,Sulfur ,Biogenesis ,Protein Binding - Abstract
SummaryHuman anamorsin was implicated in cytosolic iron-sulfur (Fe/S) protein biogenesis. Here, the structural and metal-binding properties of anamorsin and its interaction with Mia40, a well-known oxidoreductase involved in protein trapping in the mitochondrial intermembrane space (IMS), were characterized. We show that (1), anamorsin contains two structurally independent domains connected by an unfolded linker; (2), the C-terminal domain binds a [2Fe-2S] cluster through a previously unknown cysteine binding motif in Fe/S proteins; (3), Mia40 specifically introduces two disulfide bonds in a twin CX2C motif of the C-terminal domain; (4), anamorsin and Mia40 interact through an intermolecular disulfide-bonded intermediate; and (5), anamorsin is imported into mitochondria. Hence, anamorsin is the first identified Fe/S protein imported into the IMS, raising the possibility that it plays a role in cytosolic Fe/S cluster biogenesis also once trapped in the IMS.
- Published
- 2011
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