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- Title
MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria.
- Authors
Banci, Lucia; Bertini, Ivano; Cefaro, Chiara; Ciofi-Baffoni, Simone; Gallo, Angelo; Martinelli, Manuele; Sideris, Dionisia P; Katrakili, Nitsa; Tokatlidis, Kostas
- 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 α-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.
- Subjects
OXIDOREDUCTASES; CATALYSIS; OXIDATIVE stress; PROTEIN folding; MITOCHONDRIA; SUBSTRATES (Materials science); THIOREDOXIN; OXIDATION-reduction reaction
- Publication
Nature Structural & Molecular Biology, 2009, Vol 16, Issue 2, p198
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.1553