Sco Proteins Have Distinctive Roles in the CuA Center Biogenesis

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

Encuentro; 9th International Copper Meeting; 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. Recently our group proposed a mechanism for the insertion of the copper ions to the CuA center of bacterial COX, following the copper transfer reaction using NMR. Finding that 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) that act as a copper donor. In the case of humans, no homologue of PCuAC was found and biochemical studies shown several proteins involved in the assembly of the CuA center. Two of the identified proteins are Sco1 and Sco2. Structural studies showed that both proteins can act as metallochaperones because they are able to bind copper ions through a Cx3CxnH motif, and the presence of two Cys residues make them not them also able to act as thiol-disulphur oxidoreductase. The bottleneck to establish the role of each Sco in the assembly of the CuA center is the unavailability of the soluble domain of an eukaryotic COX II. Using a model of the eukaryotic oxidase (CuA*), we have been able follow the function of these two putative metallochaperones finding that Sco1 act as copper transfer protein while Sco2 is important to maintain the Cys ligands in the reduced state.