Journal article

Human glutaredoxin-1 can transfer copper to isolated metal binding domains of the P1B-type ATPase, ATP7B.

Shadi Maghool, Sharon La Fontaine, Blaine R Roberts, Ann H Kwan, Megan J Maher

Scientific Reports | Nature Publishing Group | Published : 2020

Abstract

Intracellular copper (Cu) in eukaryotic organisms is regulated by homeostatic systems, which rely on the activities of soluble metallochaperones that participate in Cu exchange through highly tuned protein-protein interactions. Recently, the human enzyme glutaredoxin-1 (hGrx1) has been shown to possess Cu metallochaperone activity. The aim of this study was to ascertain whether hGrx1 can act in Cu delivery to the metal binding domains (MBDs) of the P1B-type ATPase ATP7B and to determine the thermodynamic factors that underpin this activity. hGrx1 can transfer Cu to the metallochaperone Atox1 and to the MBDs 5-6 of ATP7B (WLN5-6). This exchange is irreversible. In a mixture of the three prote..

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Grants

Awarded by Australian Research Council


Awarded by NHMRC Dementia Leadership Fellowship


Funding Acknowledgements

This study was funded by the Australian Research Council (DP140102746 to MJM). SM was supported by an Australian Government Research Training Program Scholarship. BRR was supported by a NHMRC Dementia Leadership Fellowship (APP1138673). The support of the Florey Neuroproteomics facility and Adam Gunn for assistance in size exclusion ICP-MS data collection and analysis are also acknowledged. We acknowledge access to the biomolecular NMR facility at the School of Life and Environmental Sciences, University of Sydney.