The pivotal role of MBD4–ATP7B in the human Cu(i) excretion path as revealed by EPR experiments and all-atom simulations. Issue 7 (12th June 2019)

• Record Type: Journal Article
• Authors: Qasem, Zena; Pavlin, Matic; Ritacco, Ida; Gevorkyan-Airapetov, Lada; Magistrato, Alessandra; Ruthstein, Sharon
• Is Part Of: Metallomics. Volume 11:Issue 7(2019)
• Page Start: 1288
• Page End: 1297
• Publication Date: 2019-06-12
• Subjects: Metals -- Physiological effect -- Periodicals; 572.51
• DOI: 10.1039/c9mt00067d
• Languages: English
• ISSNs: 1756-5901

Abstract

Abstract : Atox1–MBD4 interaction mediates the in-cell Cu(i ) concentration. 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.