An NMR study of the interaction of the N-terminal cytoplasmic tail of the Wilson disease protein with copper(I)-HAH1.

ABSTRACT: ATP7B is a human P(1B)-type ATPase that has a crucial role in maintaining copper(I) homeostasis. Mutations in the corresponding gene are the cause of Wilson disease. Among its various distinguishing features is a long ( approximately 630 amino acids) N-terminal cytosolic tail containing six domains that are individually folded and capable of binding one copper(I) ion each. We expressed the entire tail as a single construct in Escherichia coli and investigated its interaction with its copper chaperone (i.e. HAH1) by solution NMR spectroscopy. We observed that all six of the metal-binding domains were metallated by Cu(I)-HAH1, with the first, the second, and the fourth domains forming an adduct with it. This behavior is different from that of the highly similar human ATPase ATP7A, in which o

SUBMITTER: Banci L 

PROVIDER: S-EPMC2666587 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature