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
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
收藏
页码:198 / 206
页数:9
相关论文
共 51 条
  • [31] Biogenesis of the essential Tim9-Tim10 chaperone complex of mitochondria - Site-specific recognition of cysteine residues by the intermembrane space receptor Mia40
    Milenkovic, Dusanka
    Gabriel, Kipros
    Guiard, Bernard
    Schulze-Specking, Agnes
    Pfanner, Nikolaus
    Chacinska, Agnieszka
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (31) : 22472 - 22480
  • [32] Precursor oxidation by Mia40 and Erv1 promotes vectorial transport of proteins into the mitochondrial intermembrane space
    Mueller, Judith M.
    Milenkovic, Dusanka
    Guiard, Bernard
    Pfanner, Nikolaus
    Chacinska, Agnieszka
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (01) : 226 - 236
  • [33] Catalysis of disulfide bond formation and isomenization in the Escherichia coli peniplasm
    Nakamoto, H
    Bardwell, JCA
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2004, 1694 (1-3): : 111 - 119
  • [34] Identification of Tim40 that mediates protein sorting to the mitochondrial intermembrane space
    Naoe, M
    Ohwa, Y
    Ishikawa, D
    Ohshima, C
    Nishikawa, S
    Yamamoto, H
    Endo, T
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (46) : 47815 - 47821
  • [35] UCSF chimera - A visualization system for exploratory research and analysis
    Pettersen, EF
    Goddard, TD
    Huang, CC
    Couch, GS
    Greenblatt, DM
    Meng, EC
    Ferrin, TE
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 2004, 25 (13) : 1605 - 1612
  • [36] The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal
    Qin, J
    Clore, GM
    Kennedy, WP
    Kuszewski, J
    Gronenborn, AM
    [J]. STRUCTURE, 1996, 4 (05) : 613 - 620
  • [37] The essential mitochondrial protein Erv1 cooperates with Mia40 in biogenesis of intermembrane space proteins
    Rissler, M
    Wiedemann, N
    Pfannschmidt, S
    Gabriel, K
    Guiard, B
    Pfanner, N
    Chacinska, A
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2005, 353 (03) : 485 - 492
  • [38] BLUE NATIVE ELECTROPHORESIS FOR ISOLATION OF MEMBRANE-PROTEIN COMPLEXES IN ENZYMATICALLY ACTIVE FORM
    SCHAGGER, H
    VONJAGOW, G
    [J]. ANALYTICAL BIOCHEMISTRY, 1991, 199 (02) : 223 - 231
  • [39] Ero1 and redox homeostasis in the endoplasmic reticulum
    Sevier, Carolyn S.
    Kaiser, Chris A.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2008, 1783 (04): : 549 - 556
  • [40] Conservation and diversity of the cellular disulfide bond formation pathways
    Sevier, Carolyn S.
    Kaiser, Chris A.
    [J]. ANTIOXIDANTS & REDOX SIGNALING, 2006, 8 (5-6) : 797 - 811