Metal Binding Domains 3 And 4 Of The Wilson Disease Protein: Solution Structure And Interaction With The Copper(I) Chaperone HAH1
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.
L. Banci, I. Bertini, F. Cantini, A. C. Rosenzweig, and Liliya A. Yatsunyk.
"Metal Binding Domains 3 And 4 Of The Wilson Disease Protein: Solution Structure And Interaction With The Copper(I) Chaperone HAH1".