Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion.

Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase / Morgada, Marcos N; Abriata, Luciano A.; Cefaro, Chiara; Gajda, Karolina; Banci, Lucia; Vila, Alejandro J.. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - STAMPA. - 112:(2015), pp. 11771-11776. [10.1073/pnas.1505056112]

Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase

CEFARO, CHIARA;GAJDA, KAROLINA;BANCI, LUCIA;
2015

Abstract

Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion.
2015
112
11771
11776
Morgada, Marcos N; Abriata, Luciano A.; Cefaro, Chiara; Gajda, Karolina; Banci, Lucia; Vila, Alejandro J.
File in questo prodotto:
File Dimensione Formato  
PNAS-2015-Morgada-11771-6.pdf

Accesso chiuso

Descrizione: articolo principale
Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 1.04 MB
Formato Adobe PDF
1.04 MB 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/2158/1013726
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 53
  • ???jsp.display-item.citation.isi??? 53
social impact