Abstract
The Wilson disease protein or ATP7B is a P 1B-type ATPase involved in human copper homeostasis. The extended N-terminus of ATP7B protrudes into the cytosol and contains six Cu(I) binding domains. This report presents the NMR structure of the polypeptide consisting of soluble Cu(I) binding domains 3 and 4. The two domains exhibit ferredoxin-like folds, are linked by a flexible loop, and act independently of one another. Domains 3 and 4 tend to aggregate in a concentration-dependent manner involving nonspecific intermolecular interactions. Both domains can be loaded with Cu(I) when provided as an acetonitrile complex or by the chaperone HAH1. HAH1 forms a 70% complex with domain 4 that is in fast exchange with the free protein in solution. The ability of HAH1 to form a complex only with some domains of ATP7B is an interesting property of this class of proteins and may have a signaling role in the function of the ATPases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / chemistry*
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / isolation & purification
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Adenosine Triphosphatases / metabolism*
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Apoproteins / chemistry
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Apoproteins / metabolism
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Cation Transport Proteins / chemistry*
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Cation Transport Proteins / genetics
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Cation Transport Proteins / isolation & purification
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Cation Transport Proteins / metabolism*
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Copper / metabolism*
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Copper Transport Proteins
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Copper-Transporting ATPases
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Gene Amplification
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Homeostasis
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Humans
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Metallochaperones
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Models, Molecular
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Molecular Chaperones / metabolism*
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Peptide Fragments / chemistry
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Peptide Fragments / isolation & purification
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Peptide Fragments / metabolism
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Polymerase Chain Reaction
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Protein Conformation
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Solubility
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Solutions
Substances
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ATOX1 protein, human
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Apoproteins
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Cation Transport Proteins
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Copper Transport Proteins
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Metallochaperones
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Molecular Chaperones
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Peptide Fragments
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Solutions
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Copper
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Adenosine Triphosphatases
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ATP7B protein, human
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Copper-Transporting ATPases