MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria

Banci, L., Bertini, I., Cefaro, C., Ciofi-Baffoni, S., Gallo, A., Martinelli, M., Sideris, D.P., Katrakili, N. and Tokatlidis, K. (2009) MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria. Nature Structural and Molecular Biology, 16(2), pp. 198-206. (doi:10.1038/nsmb.1553)

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Abstract

MIA40 has a key role in oxidative protein folding in the mitochondrial intermembrane space. We present the solution structure of human MIA40 and its mechanism as a catalyst of oxidative folding. MIA40 has a 66-residue folded domain made of an -helical hairpin core stabilized by two structural disulfides and a rigid N-terminal lid, with a characteristic CPC motif that can donate its disulfide bond to substrates. The CPC active site is solvent-accessible and sits adjacent to a hydrophobic cleft. Its second cysteine (Cys55) is essential in vivo and is crucial for mixed disulfide formation with the substrate. The hydrophobic cleft functions as a substrate binding domain, and mutations of this domain are lethal in vivo and abrogate binding in vitro. MIA40 represents a thioredoxin-unrelated, minimal oxidoreductase, with a facile CPC redox active site that ensures its catalytic function in oxidative folding in mitochondria.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tokatlidis, Professor Kostas
Authors: Banci, L., Bertini, I., Cefaro, C., Ciofi-Baffoni, S., Gallo, A., Martinelli, M., Sideris, D.P., Katrakili, N., and Tokatlidis, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Nature Structural and Molecular Biology
Publisher:Nature Publishing Group
ISSN:1545-9993
ISSN (Online):1545-9985

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