CPL - Chalmers Publication Library
| Utbildning | Forskning | Styrkeområden | Om Chalmers | In English In English Ej inloggad.

The six metal binding domains in human copper transporter, ATP7B: molecular biophysics and disease-causing mutations

Candan Ariöz (Institutionen för biologi och bioteknik, Kemisk biologi) ; Y. Z. Li ; Pernilla Wittung-Stafshede (Institutionen för biologi och bioteknik, Kemisk biologi)
Biometals (0966-0844). Vol. 30 (2017), 6, p. 823-840.
[Artikel, refereegranskad vetenskaplig]

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

Nyckelord: Wilson disease, ATP7B, Atox1, Metal-binding domains, Cu transport, Disease-causing mutations, n-terminal domain, sodium-potassium pump, human wilson protein, ray-absorption spectroscopy, atpase atp7b, crystal-structure, menkes-disease, chaperone hah1, in-vitro, intracellular trafficking

Denna post skapades 2017-12-13. Senast ändrad 2018-01-17.
CPL Pubid: 253754


Läs direkt!

Länk till annan sajt (kan kräva inloggning)

Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Kemisk biologi


Biokemi och molekylärbiologi

Chalmers infrastruktur