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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Absorptiometry, Photon
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Adenosine Triphosphatases / chemistry
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Amino Acid Motifs / physiology
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Archaeal Proteins / chemistry*
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Archaeal Proteins / genetics
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Archaeal Proteins / metabolism
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Archaeoglobus fulgidus / chemistry*
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Archaeoglobus fulgidus / genetics
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Archaeoglobus fulgidus / metabolism
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Binding Sites / physiology
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Cation Transport Proteins / chemistry
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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Copper / chemistry*
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Copper / metabolism
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Copper-Transporting ATPases
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Cysteine / chemistry
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Cysteine / genetics
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Cysteine / metabolism
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Electron Spin Resonance Spectroscopy
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Ion Transport / physiology
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Iron / chemistry
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Iron / metabolism
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Metalloproteins / chemistry*
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Metalloproteins / genetics
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Metalloproteins / metabolism
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Models, Molecular
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Molecular Chaperones / chemistry*
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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Oxidation-Reduction
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Sequence Homology, Amino Acid
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Structure-Activity Relationship
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Zinc / chemistry*
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Zinc / metabolism
Substances
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Archaeal Proteins
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Cation Transport Proteins
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Metalloproteins
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Molecular Chaperones
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Copper
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Iron
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Adenosine Triphosphatases
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Copper-Transporting ATPases
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Zinc
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Cysteine