A hint for the function of human Sco1 from different structures

Abstract

The solution structures of apo, Cu(I), and Ni(II) human Sco1 have been determined. The protein passes from an open and conformationally mobile state to a closed and rigid conformation upon metal binding as shown by electrospray ionization MS and NMR data. The metal ligands of Cu(l) are two Cys residues of the CPXXCP motif and a His residue. The latter is suitably located to coordinate the metal anchored by the two Cys residues. The coordination sphere of Ni(II) in solution is completed by another ligand, possibly Asp. Crystals of the Ni(II) derivative were also obtained with the Ni(II) ion bound to the same His residue and to the two oxidized Cys residues of the CPXXCP motif. We propose that the various structures solved here represent the various states of the protein in its functional cycle and that the metal can be bound to the oxidized protein at a certain stage. Although it now seems reasonable that Sco1, which is characterized by a thioredoxin fold, has evolved to bind a metal atom via the di-Cys motif to act as a copper chaperone, the oxidized form of the nickel-bound protein suggests that it may also maintain the thioredoxin function

Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of Cu A in human cytochrome oxidase

“…Human Sco1, human Sco2, and Tt Sco1 were expressed in Escherichia coli BL21-Gold (DE3) cells (Stratagene) to high levels in LB medium. The purification of each protein in its apo form was done as described (24,26,32). COX II* and Tt COX II were expressed in E. coli Bl21-Gold (DE3) cells (Stratagene).…”

“…Sco1 and Sco2 are homologous proteins, anchored to the inner mitochondrial membrane through a single transmembrane helix that locates their soluble, copper-binding domain in the IMS (15,23). Both proteins share a thioredoxin fold and bind copper ions through a functional CX 3 C motif complemented by a histidine residue located in a β-hairpin absent in thioredoxins (24)(25)(26)(27). This CX 3 CX n H motif allows Sco proteins either to bind Cu(I) with high affinity or to act as thioloxidoreductases (27)(28)(29).…”

Evidence for a Pro-oxidant Intermediate in the Assembly of Cytochrome Oxidase

“…The structure of the Cu(I)-Sco1 complex was subsequently achieved by NMR spectroscopy (13). The inability to crystallize Sco1 with a bound Cu(I) led some investigators to speculate that Sco1 might function in CcO assembly independent of Cu(I) binding (7,12).…”

Revealing ETC-1922159 Affected Unknown 3<em>^rd</em> order WNT10B-X-X Combinations, in Silico

“…The metallation of COX II occurs at an early stage of COX assembly and is required for the incorporation of this structural subunit into the assembling holoenzyme. To confirm the matter, different configurations of SCO1 have been found to be existant while interacting with COX II, for copper transfer 50 .…”