2K3J

The solution structure of human Mia40

Summary for 2K3J

• Entry DOI: 10.2210/pdb2k3j/pdb
• NMR Information: BMRB: 15763
• Descriptor: Mitochondrial intermembrane space import and assembly protein 40 (1 entity in total)
• Functional Keywords: alpha-hairpin fold, coiled coil-helix-coiled coil-helix domain, mitochondrial oxidase, protein import and folding, alternative splicing, mitochondrion, protein transport, translocation, transport, oxidoreductase
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 16403.76

Authors

Ciofi Baffoni, S.,Bertini, I.,Gallo, A. (deposition date: 2008-05-08, release date: 2009-02-10, Last modification date: 2024-11-20)

Primary citation

Banci, L.,Bertini, I.,Cefaro, C.,Ciofi-Baffoni, S.,Gallo, A.,Martinelli, M.,Sideris, D.P.,Katrakili, N.,Tokatlidis, K.
MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria.
Nat.Struct.Mol.Biol., 16:198-206, 2009

PubMed 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 alpha-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.

PubMed: 19182799
DOI: 10.1038/nsmb.1553

Experimental method

SOLUTION NMR