MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria

被引：216

作者：

Banci, Lucia ^{[1
,2
]}

Bertini, Ivano ^{[1
,2
]}

Cefaro, Chiara ^{[1
,2
]}

Ciofi-Baffoni, Simone ^{[1
,2
]}

Gallo, Angelo ^{[1
,2
]}

Martinelli, Manuele ^{[1
,2
]}

Sideris, Dionisia P. ^{[3
,4
]}

Katrakili, Nitsa ^{[3
]}

Tokatlidis, Kostas ^{[3
,5
]}

机构：

[1] Univ Florence, Magnet Resonance Ctr, CERM, I-50019 Florence, Italy

[2] Univ Florence, Dept Chem, I-50019 Florence, Italy

[3] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece

[4] Univ Crete, Dept Biol, Iraklion 71409, Crete, Greece

[5] Univ Crete, Dept Mat Sci & Technol, Iraklion 71003, Crete, Greece

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2009年 / 16卷 / 02期

关键词：

DISULFIDE BOND FORMATION; INTERMEMBRANE SPACE PROTEINS; NMR STRUCTURE DETERMINATION; RELAY SYSTEM; CYTOCHROME-C; RESPIRATORY-CHAIN; CHEMICAL-SHIFTS; IMPORT PATHWAY; CHAPERONE; ERV1;

D O I：

10.1038/nsmb.1553

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：198 / 206

页数：9