Crystallization and preliminary X-ray studies of the N-domain of the Wilson disease associated protein

Wilson disease associated protein (ATP7B) is essential for copper transport in human cells. Mutations that affect ATP7B function result in Wilson's disease, a chronic copper toxicosis. Disease-causing mutations within the N-domain of ATP7B (WND) are known to disrupt ATP binding, but a high-resolution X-ray structure of the ATP-binding site has not been reported. The N-domain was modified to delete the disordered loop comprising residues His1115–Asp1138 (WNDΔ_1115–1138). Unlike the wild-type N-domain, WNDΔ_1115–1138 formed good-quality crystals. Synchrotron diffraction data have been collected from WNDΔ_1115–1138 at the Canadian Light Source. A native WNDΔ_1115–1138 crystal diffracted to 1.7 Å resolution and belonged to space group P4₂2₁2, with unit-cell parameters a = 39.2, b = 39.2, c = 168.9 Å. MAD data were collected to 2.7 Å resolution from a SeMet-derivative crystal with unit-cell parameters a = 38.4, b = 38.4, c = 166.7 Å. The WNDΔ_1115–1138 structure is likely to be solved by phasing from multiwavelength anomalous diffraction (MAD) experiments.