Journal:JBIC:6

Sco Proteins are Involved in Electron Transfer Processes

Lucia Banci, Ivano Bertini, Simone Ciofi-Baffoni, Tatiana Kozyreva, Mirko Mori and Shenlin Wang ^[1]

Molecular Tour
        Sco is a family of proteins ubiquitous to all kingdoms of life. Ortholog and paralog genome browsing has shown that more than one representative of this class are often present in bacterial and eukaryotic genomes. They have a thioredoxin-like fold and bind a single Cu(I) or Cu(II) ion through a CXXXC motif and a conserved His ligand, with both tight and weak affinities. They have been implicated in the assembly of the CuA site of cytochrome c oxidase as copper chaperones and/or thioredoxins. Starting from our previous bioinformatic analysis of Sco proteins encoded in prokaryotic genomes we focused on the genome of Pseudomonas putida KT2440, which contains six Sco like sequences in different genomic contexts. The protein named pp3183 has been chosen as a target since it is formed by a Sco domain fused to a well-known electron transfer protein, cyt c, this system being potentially involved in electron transfer processes. The solution structures of both Sco domains and cyt c, separately expressed, were determined and their copper binding/electron transfer properties were investigated.

        The thioredoxin-like Sco domain of pp3183 does not bind copper(II), binds copper(I) with weak affinity without involving the conserved His, and has redox properties consisting of thioredoxin activity and the ability of reducing copper(II) to copper(I), and iron(III) to iron(II) in the cyt c domain. These findings indicate that the His ligand coordination is the discriminating factor for introducing a metallochaperone function in a thioredoxin-like fold, typically responsible of electron transfer processes. A comparative structural analysis of the Sco domain from P. putida vs. eukaryotic Sco proteins revealed structural determinants affecting the formation of a tight vs. weak affinity copper binding site in Sco proteins. In ppSco proteins, the CXXXC motif and His-ligand are surrounded by neighboring polar residues. Eukaryotic Sco proteins possess the same conserved CXXXC motif and neighboring copper binding His residue as is found in P. putida Sco proteins. Hydrophobic interactions between the CXXXC region and the conserved His region freeze the copper binding state conformation only in eukaryotic Scos determining a tight affinity binding site.

PDB reference: Cytochrome c domain of pp3183 protein from Pseudomonas putida, 2l4d.