Issue 7, 2019

The pivotal role of MBD4–ATP7B in the human Cu(i) excretion path as revealed by EPR experiments and all-atom simulations

Abstract

Copper's essentiality and toxicity require a meticulous mechanism for its acquisition, cellular distribution and excretion, which remains hitherto elusive. Herein, we jointly employed electron paramagnetic resonance spectroscopy and all-atom simulations to resolve the copper trafficking mechanism in humans considering the route travelled by Cu(I) from the metallochaperone Atox1 to the metal binding domains 3 and 4 of ATP7B. Our study shows that Cu(I) in the final part of its extraction pathway is most likely mediated by binding of Atox1 monomer to MBD4 of ATP7B. This interaction takes place through weak metal-stabilized protein–protein interactions.

Graphical abstract: The pivotal role of MBD4–ATP7B in the human Cu(i) excretion path as revealed by EPR experiments and all-atom simulations

Supplementary files

Article information

Article type
Paper
Submitted
24 3 2019
Accepted
24 5 2019
First published
12 6 2019
This article is Open Access
Creative Commons BY license

Metallomics, 2019,11, 1288-1297

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