ANALYSIS OF FUNCTIONAL DOMAINS OF WILSON-DISEASE PROTEIN (ATP7B) IN SACCHAROMYCES-CEREVISIAE

Wilson disease is a genetic disorder of copper metabolism characterize d by the toxic accumulation of copper in the liver. The ATP7B gene, wh ich encodes a copper transporting P-type ATPase, is defective in patie nts with Wilson disease. To investigate the function of ATP7B, wild ty pe or mutated ATP7B cDNA was introduced into a yeast strain larking th e CCC2 gene (Delta ccc2), the yeast homologue of of ATP7B. Wild type a nd the H1069Q mutant could rescue Delta ccc2, however, the N1270S muta nt could not, reflecting phenotypic variability of Wilson disease. In addition, the mutant containing only the sixth copper binding domain c ould rescue Delta ccc2, indicating its functional importance. (C) 1998 Federation of European Biochemical Societies.