Biochemistry

Extracting Copper

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Science  26 Apr 2002:
Vol. 296, Issue 5568, pp. 619-621
DOI: 10.1126/science.296.5568.619e

In Enterococcus hirae, the cop operon encodes the copper chaperone CopZ and the transcription factor CopY. At low ambient copper, CopY binds Zn(II) and blocks expression of the entire operon; when copper is present, CopZ delivers Cu(I) to CopY, displacing Zn(II) and relieving transcriptional repression. The CopZ metal-binding domain is similar to those of two human proteins: the copper chaperone CCS and the copper-transporting ATPase MNK (mutation in which gives rise to Menkes' disease).

Cobine et al. show that CopZ carries Cu(I) in a mix of two- and three-coordinate states, partly exposed to solvent and thus susceptible to displacement by thiolate ligands of CopY. On the other hand, CopY binds its two Cu(I) atoms tightly in a solvent-shielded binuclear trigonal arrangement. Despite their overall structural similarity, the copper-binding domain of the Menkes protein, MNKr2, cannot donate its Cu(I) to CopY in the same fashion as CopZ. Nevertheless, converting four surface residues of MNKr2 to lysines enabled it to transfer copper, demonstrating that the key specificity determinant is electrostatic docking. This surface complementarity is reminiscent of the interaction between the chaperone CCS and its target, superoxide dismutase (mutations in which are linked to familial amyotrophic lateral sclerosis), as described by Lamb et al.GJC

Biochemistry 10.1021/bi025515c (2002); Nature Struct. Biol.8, 750 (2001).

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