The six metal binding domains in human copper transporter, ATP7B: molecular biophysics and disease-causing mutations
Artikel i vetenskaplig tidskrift, 2017

Wilson Disease (WD) is a hereditary genetic disorder, which coincides with a dysfunctional copper (Cu) metabolism caused by mutations in ATP7B, a membrane-bound P-1B-type ATPase responsible for Cu export from hepatic cells. The N-terminal part (similar to 600 residues) of the multi-domain 1400-residue ATP7B constitutes six metal binding domains (MBDs), each of which can bind a copper ion, interact with other ATP7B domains as well as with different proteins. Although the ATP7B's MBDs have been investigated in vitro and in vivo intensively, it remains unclear how these domains modulate overall structure, dynamics, stability and function of ATP7B. The presence of six MBDs is unique to mammalian ATP7B homologs, and many WD causing missense mutations are found in these domains. Here, we have summarized previously reported in vitro biophysical data on the MBDs of ATP7B and WD point mutations located in these domains. Besides the demonstration of where the research field stands today, this review showcasts the need for further biophysical investigation about the roles of MBDs in ATP7B function. Molecular mechanisms of ATP7B are important not only in the development of new WD treatment but also for other aspects of human physiology where Cu transport plays a role. RAHAMS JP, 1994, NATURE, V370, P621


ray-absorption spectroscopy

sodium-potassium pump

chaperone hah1

Metal-binding domains

human wilson protein

n-terminal domain

atpase atp7b


intracellular trafficking



Cu transport

Wilson disease


Disease-causing mutations


Candan Ariöz

Chalmers, Biologi och bioteknik, Kemisk biologi

Y. Z. Li

Umeå universitet

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi


0966-0844 (ISSN) 1572-8773 (eISSN)

Vol. 30 6 823-840


Biokemi och molekylärbiologi



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