Characterization and structure of a Zn2+ and [2Fe-2S]-containing copper chaperone from Archaeoglobus fulgidus. Academic Article uri icon

abstract

  • Bacterial CopZ proteins deliver copper to P1B-type Cu+-ATPases that are homologous to the human Wilson and Menkes disease proteins. The genome of the hyperthermophile Archaeoglobus fulgidus encodes a putative CopZ copper chaperone that contains an unusual cysteine-rich N-terminal domain of 130 amino acids in addition to a C-terminal copper binding domain with a conserved CXXC motif. The N-terminal domain (CopZ-NT) is homologous to proteins found only in extremophiles and is the only such protein that is fused to a copper chaperone. Surprisingly, optical, electron paramagnetic resonance, and x-ray absorption spectroscopic data indicate the presence of a [2Fe-2S] cluster in CopZ-NT. The intact CopZ protein binds two copper ions, one in each domain. The 1.8 A resolution crystal structure of CopZ-NT reveals that the [2Fe-2S] cluster is housed within a novel fold and that the protein also binds a zinc ion at a four-cysteine site. CopZ can deliver Cu+ to the A. fulgidus CopA N-terminal metal binding domain and is capable of reducing Cu2+ to Cu+. This unique fusion of a redox-active domain with a CXXC-containing copper chaperone domain is relevant to the evolution of copper homeostatic mechanisms and suggests new models for copper trafficking.

published proceedings

  • J Biol Chem

altmetric score

  • 1

author list (cited authors)

  • Sazinsky, M. H., LeMoine, B., Orofino, M., Davydov, R., Bencze, K. Z., Stemmler, T. L., ... Rosenzweig, A. C

citation count

  • 31

complete list of authors

  • Sazinsky, Matthew H||LeMoine, Benjamin||Orofino, Maria||Davydov, Roman||Bencze, Krisztina Z||Stemmler, Timothy L||Hoffman, Brian M||Argüello, José M||Rosenzweig, Amy C

publication date

  • July 2007