Arabidopsis thaliana Hcc1 is a Sco-like metallochaperonefor Cu A assembly in Cytochrome c Oxidase

The assembly of the CuA site in Cytochrome c Oxidase (COX) is a criticalstep for aerobic respiration in COX-dependent organisms. Several geneproducts have been associated with the assembly of this copper site, themost conserved of them belonging to the Sco family of proteins, whichhave been shown to perform different roles in different organisms. Plantsexpress two orthologs of Sco proteins: Hcc1 and Hcc2. Hcc1 is known tobe essential for plant development and for COX maturation, but its precisefunction has not been addressed until now. Here, we report the biochemi-cal, structural and functional characterization of Arabidopsis thaliana Hcc1protein (here renamed Sco1). We solved the crystal structure of the Cu+1-bound soluble domain of this protein, revealing a tri coordinated environ-ment involving a CxxxCxnH motif. We show that AtSco1 is able to workas a copper metallochaperone, inserting two Cu+1 ions into the CuA site ina model of CoxII. We also show that AtSco1 does not act as a thiol-disul-fide oxido-reductase. Overall, this information sheds new light on the bio-chemistry of Sco proteins, highlighting the diversity of functions amongthem despite their high structural similarities.