Biogenesis of copper sites in heme-copper oxidases: A theme with variations

LLASES, MARÍA EUGENIA; MORGADA, MARCOS; A. J. VILA

Encuentro; Latin American Protein Society Meeting; 2019

Copper is anessential cofactor in all life1. Due to its redox activity and coordination features, it is auseful cofactor for many redox reactions. However, these same properties causeits toxicity, since it can generate ROS and bind to adventitious sites. Cellshave evolved extensive proteins networks in order to handle copper ions2. Cytochrome c oxidase (COX) is the terminal oxidasein most aerobic organisms. This enzymatic complex catalyzes electron transferfrom cytochrome c to molecularoxygen. It requires four redox cofactors, two of them being copper sites: CuAand CuB3.Sco?s arethiorredoxin-related proteins that can bind copper and are highly conservedamong all organisms. They have been generally related with thiol-oxidoreductaseactivity and copper insertion in CuA biogenesis, although otherfunctions have also been proposed4.We analyzed thebiogenesis of CuA site in COX from several organisms and examinedthe variations in the biochemical mechanisms of assembly. We showed that Scoproteins can act as thiol-reductases for the coordinating cysteines in CuA5,6, and also as specific metallochaperones, inserting two Cu(I) ionsinto the copper site4,6.It was generallyassumed that copper in cells is handled as Cu(I), however, recent evidencepoints to Cu(II) as the relevant copper species in COX assembly mechanisms inbacteria7. Here we address the biochemical viability of Cu(II) insertion in Arabidopsis thaliana CuA site,and the mechanistic features of the process. This data opens up new questionsregarding the biological relevance of Cu(II) transport and insertion inmitochondria.