Anamorsin is a [2Fe-2S] cluster-containing substrate of the Mia40-dependent mitochondrial protein trapping machinery

Banci, L., Bertini, I., Ciofi-Baffoni, S., Boscaro, F., Chatzi, A., Mikolajczyk, M., Tokatlidis, K. and Winkelmann, J. (2011) Anamorsin is a [2Fe-2S] cluster-containing substrate of the Mia40-dependent mitochondrial protein trapping machinery. Chemistry and Biology, 18(6), pp. 794-804. (doi: 10.1016/j.chembiol.2011.03.015) (PMID:21700214)

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 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tokatlidis, Professor Kostas and Chatzi, Ms Afroditi
• Authors: Banci, L., Bertini, I., Ciofi-Baffoni, S., Boscaro, F., Chatzi, A., Mikolajczyk, M., Tokatlidis, K., and Winkelmann, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Chemistry and Biology
• Publisher: Cell Press
• ISSN: 1074-5521
• ISSN (Online): 1879-1301
• Published Online: 23 June 2011