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.

MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria / L.Banci; I.Bertini; C.Cefaro; S.Ciofi-Baffoni; A.Gallo; M.Martinelli; D.P.Sideris; N.Katrakili; K.Tokatlidis. - In: NATURE STRUCTURAL & MOLECULAR BIOLOGY. - ISSN 1545-9993. - STAMPA. - 16:(2009), pp. 198-206. [10.1038/nsmb.1553]

MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria

BANCI, LUCIA;BERTINI, IVANO;CEFARO, CHIARA;CIOFI BAFFONI, SIMONE;GALLO, ANGELO;MARTINELLI, MANUELE;
2009

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.
2009
16
198
206
L.Banci; I.Bertini; C.Cefaro; S.Ciofi-Baffoni; A.Gallo; M.Martinelli; D.P.Sideris; N.Katrakili; K.Tokatlidis
File in questo prodotto:
File Dimensione Formato  
MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 999.27 kB
Formato Adobe PDF
999.27 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/353863
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 215
  • ???jsp.display-item.citation.isi??? 219
social impact