How do Sco Proteins Score the COX??

MORGADA, MARCOS; ABRIATA LA; A. J. VILA

Congreso; XLIII Reunión Annual de la Sociedad Argentina de Biofísica; 2014

The dinuclear copper center CuA is the electron entry point of the cytochrome c oxidase (COX) and the correct assembly of this metal center is essential for the function of the complex and thus for the survival of the cell. Following the copper transfer reactions using NMR, our group proposed a mechanism for the insertion of the copper ions to the CuA center of bacterial COX. Bacterial Sco, despite its ability to bind copper ions, keeps the cysteines from the CuA center in the reduced state thus the copper ions can be transferred from a periplasmic metallochaperone (PCuAC). In the case of humans, biochemical studies shown several proteins involved in the assembly of COX. Two of the identified proteins, Sco1 and Sco2 are directly involved in the formation of the CuA center in subunit II (COX II) and structural studies showed that both proteins can act as metallochaperones or as thiol-disulphur oxidoreductases since both proteins has two Cys residues in their copper biding site. The unavailability of the soluble domain of an eukaryotic COX II has stalled further investigation but using a model of the eukaryotic oxidase (COX II*), we have been able to assess the function of these Sco proteins finding that Sco1 act as copper transfer protein while Sco2 is crucial in the maintenance of the cysteines redox state homeostasis.