An EPR study on the interaction between the Cu(I) metal binding domains of ATP7B and the Atox1 metallochaperone

Michael Zaccak; Zena Qasem; Lada Gevorkyan-Airapetov; Sharon Ruthstein

doi:10.3390/ijms21155536

An EPR study on the interaction between the Cu(I) metal binding domains of ATP7B and the Atox1 metallochaperone

Michael Zaccak, Zena Qasem, Lada Gevorkyan-Airapetov, Sharon Ruthstein

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Copper’s essentiality and toxicity mean it requires a sophisticated regulation system for its acquisition, cellular distribution and excretion, which until now has remained elusive. Herein, we applied continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy in solution to resolve the copper trafficking mechanism in humans, by considering the route travelled by Cu(I) from the metallochaperone Atox1 to the metal binding domains of ATP7B. Our study revealed that Cu(I) is most likely mediated by the binding of the Atox1 monomer to metal binding domain 1 (MBD1) and MBD4 of ATP7B in the final part of its extraction pathway, while the other MBDs mediate this interaction and participate in copper transfer between the various MBDs to the ATP7B membrane domain. This research also proposes that MBD1-3 and MBD4-6 act as two independent units.

Original language	English
Article number	5536
Pages (from-to)	1-13
Number of pages	13
Journal	International Journal of Molecular Sciences
Volume	21
Issue number	15
DOIs	https://doi.org/10.3390/ijms21155536
State	Published - 2 Aug 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Funding

Funding: This research was funded by ERC-Stg, grant number 754365.

Funders	Funder number
ERC-STG
Horizon 2020 Framework Programme	754365

Keywords

ATP7B
Atox1
Copper metabolism
DEER
EPR
Metal binding domains

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10.3390/ijms21155536

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abstract = "Copper{\textquoteright}s essentiality and toxicity mean it requires a sophisticated regulation system for its acquisition, cellular distribution and excretion, which until now has remained elusive. Herein, we applied continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy in solution to resolve the copper trafficking mechanism in humans, by considering the route travelled by Cu(I) from the metallochaperone Atox1 to the metal binding domains of ATP7B. Our study revealed that Cu(I) is most likely mediated by the binding of the Atox1 monomer to metal binding domain 1 (MBD1) and MBD4 of ATP7B in the final part of its extraction pathway, while the other MBDs mediate this interaction and participate in copper transfer between the various MBDs to the ATP7B membrane domain. This research also proposes that MBD1-3 and MBD4-6 act as two independent units.",

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AU - Ruthstein, Sharon

PY - 2020/8/2

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AB - Copper’s essentiality and toxicity mean it requires a sophisticated regulation system for its acquisition, cellular distribution and excretion, which until now has remained elusive. Herein, we applied continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy in solution to resolve the copper trafficking mechanism in humans, by considering the route travelled by Cu(I) from the metallochaperone Atox1 to the metal binding domains of ATP7B. Our study revealed that Cu(I) is most likely mediated by the binding of the Atox1 monomer to metal binding domain 1 (MBD1) and MBD4 of ATP7B in the final part of its extraction pathway, while the other MBDs mediate this interaction and participate in copper transfer between the various MBDs to the ATP7B membrane domain. This research also proposes that MBD1-3 and MBD4-6 act as two independent units.

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KW - Atox1

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KW - DEER

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An EPR study on the interaction between the Cu(I) metal binding domains of ATP7B and the Atox1 metallochaperone

Abstract

Bibliographical note

Funding

Keywords

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