Human copper-transporting ATPase ATP7B (The Wilson's Disease Protein): Biochemical properties and regulation

Svetlana Lutsenko, Roman G. Efremov, Ruslan Tsivkovskii, Joel M. Walker

Research output: Contribution to journalArticle

Abstract

Wilson's disease protein (WNDP) is a product of a gene ATP7B that is mutated in patients with Wilson's disease, a severe genetic disorder with hepatic and neurological manifestations caused by accumulation of copper in the liver and brain. In a cell, WNDP transports copper across various cell membranes using energy of ATP-hydrolysis. Copper regulates WNDP at several levels, modulating its catalytic activity, posttranslational modification, and intracellular localization. This review summarizes recent studies on enzymatic function and copper-dependent regulation of WNDP. Specifically, we describe the molecular architecture and major biochemical properties of WNDP, discuss advantages of the recently developed functional expression of WNDP in insect cells, and summarize the results of the ligand-binding studies and molecular modeling experiments for the ATP-binding domain of WNDP. In addition, we speculate on how copper binding may regulate the activity and intracellular distribution of WNDP, and what role the human copper chaperone Atox1 may play in these processes.

Original languageEnglish (US)
Pages (from-to)351-362
Number of pages12
JournalJournal of Bioenergetics and Biomembranes
Volume34
Issue number5
DOIs
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Copper
Adenosine Triphosphate
Hepatolenticular Degeneration
Inborn Genetic Diseases
Wilson disease protein
copper-transporting ATPases
Liver
Protein Transport
Post Translational Protein Processing
Neurologic Manifestations
Insects
Hydrolysis
Cell Membrane
Ligands
Brain
Genes

Keywords

  • ATP-binding
  • ATP7B
  • Copper
  • Molecular modeling
  • P-type ATPase
  • Regulation
  • Wilson's disease

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Human copper-transporting ATPase ATP7B (The Wilson's Disease Protein) : Biochemical properties and regulation. / Lutsenko, Svetlana; Efremov, Roman G.; Tsivkovskii, Ruslan; Walker, Joel M.

In: Journal of Bioenergetics and Biomembranes, Vol. 34, No. 5, 10.2002, p. 351-362.

Research output: Contribution to journalArticle

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