title: Anamorsin is a [2Fe-2S] cluster-containing substrate of the Mia40-dependent mitochondrial protein trapping machinery.
abstract: Human 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 CX(2)C 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.
authors.affiliation: Magnetic Resonance Center CERM, University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy. banci@cerm.unifi.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.forename: Ivano
authors.initials: I
authors.lastname: Bertini
authors.forename: Simone
authors.initials: S
authors.lastname: Ciofi-Baffoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Boscaro
authors.forename: Afroditi
authors.initials: A
authors.lastname: Chatzi
authors.forename: Maciej
authors.initials: M
authors.lastname: Mikolajczyk
authors.forename: Kostas
authors.initials: K
authors.lastname: Tokatlidis
authors.forename: Julia
authors.initials: J
authors.lastname: Winkelmann
mesh_terms: D003545:Cysteine; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010084:Oxidation-Reduction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013455:Sulfur / Q000378:metabolism
chemical_list: C507282:CHCHD4 protein, human; C489114:CIAPIN1 protein, human; C531900:Dre2 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D007506:Iron-Sulfur Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; D013455:Sulfur; D007501:Iron; D003545:Cysteine