The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations

Ariel R. Levy; Meital Turgeman; Lada Gevorkyan‐Aiapetov; Sharon Ruthstein

doi:10.1002/pro.3197

journal article May 31, 2017

The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations

Ariel R. Levy Meital Turgeman Lada Gevorkyan‐Aiapetov Sharon Ruthstein

Protein Science Vol. 26 No. 8 pp. 1609-1618 · Wiley

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Abstract

AbstractMetallochaperones are responsible for shuttling metal ions to target proteins. Thus, a metallochaperone's structure must be sufficiently flexible both to hold onto its ion while traversing the cytoplasm and to transfer the ion to or from a partner protein. Here, we sought to shed light on the structure of Atox1, a metallochaperone involved in the human copper regulation system. Atox1 shuttles copper ions from the main copper transporter, Ctr1, to the ATP7b transporter in the Golgi apparatus. Conventional biophysical tools such as X‐ray or NMR cannot always target the various conformational states of metallochaperones, owing to a requirement for crystallography or low sensitivity and resolution. Electron paramagnetic resonance (EPR) spectroscopy has recently emerged as a powerful tool for resolving biological reactions and mechanisms in solution. When coupled with computational methods, EPR with site‐directed spin labeling and nanoscale distance measurements can provide structural information on a protein or protein complex in solution. We use these methods to show that Atox1 can accommodate at least four different conformations in the apo state (unbound to copper), and two different conformations in the holo state (bound to copper). We also demonstrate that the structure of Atox1 in the holo form is more compact than in the apo form. Our data provide insight regarding the structural mechanisms through which Atox1 can fulfill its dual role of copper binding and transfer.

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Details

Published: May 31, 2017
Vol/Issue: 26(8)
Pages: 1609-1618
License: View

Authors

A

Ariel R. Levy

The Department of Chemistry, Faculty of Exact Science Bar Ilan University Ramat‐Gan 5290002 Israel

M

Meital Turgeman

The Department of Chemistry, Faculty of Exact Science Bar Ilan University Ramat‐Gan 5290002 Israel

L

Lada Gevorkyan‐Aiapetov

The Department of Chemistry, Faculty of Exact Science Bar Ilan University Ramat‐Gan 5290002 Israel

S

Sharon Ruthstein

The Department of Chemistry, Faculty of Exact Science Bar Ilan University Ramat‐Gan 5290002 Israel

Funding

Israel Science Foundation Award: 280/12

Cite This Article

Ariel R. Levy, Meital Turgeman, Lada Gevorkyan‐Aiapetov, et al. (2017). The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations. Protein Science, 26(8), 1609-1618. https://doi.org/10.1002/pro.3197

The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations

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