Solution structure of domains 3 and 4 of human ATP7B
[ATP7B_HUMAN] Defects in ATP7B are the cause of Wilson disease (WD) [MIM:277900]. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.                                                  
[ATP7B_HUMAN] Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
Publication Abstract from PubMed
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.
Metal binding domains 3 and 4 of the Wilson disease protein: solution structure and interaction with the copper(I) chaperone HAH1.,Banci L, Bertini I, Cantini F, Rosenzweig AC, Yatsunyk LA Biochemistry. 2008 Jul 15;47(28):7423-9. Epub 2008 Jun 18. PMID:18558714
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.