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Issue 11, 2013
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Conserved residue modulates copper-binding properties through structural dynamics in human copper chaperone Atox1

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Abstract

The human copper chaperone Atox1 plays a central role in the transport of copper in cells. It has been reported that the conserved residue Lys60 contributes to the heterocomplex stability of Atox1 with its target protein ATPase, and that the K60A mutation could diminish the copper transfer. In this work, we carried out the structure determination and dynamic analysis of Atox1 with the K60A mutation in order to elucidate the role of the conserved residue Lys60 in the copper transport. Results show that the K60A mutation results in crucial secondary structure rearrangements and side-chain orientation alteration of the metal-binding residues in Atox1. Protein dynamic studies reveal that the K60A mutation leads to increased overall flexibility, and a significant difference in dynamic properties of the metal-binding sites. The structure and dynamic changes cause a decrease in the copper-binding stability of the K60A mutant. In addition, Cu(I)-mediated hetero-protein interactions with ATP7A are present in the metal transfer of both Atox1 variants, although copper transfer is accompanied with smaller structural alteration in the K60A mutant. These results indicate that Lys60 is crucial in maintaining the structure and dynamic properties of Atox1.

Graphical abstract: Conserved residue modulates copper-binding properties through structural dynamics in human copper chaperone Atox1

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Publication details

The article was received on 07 Jul 2013, accepted on 13 Aug 2013 and first published on 14 Aug 2013


Article type: Paper
DOI: 10.1039/C3MT00190C
Metallomics, 2013,5, 1566-1573

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    Conserved residue modulates copper-binding properties through structural dynamics in human copper chaperone Atox1

    Z. Xi, C. Shi, C. Tian and Y. Liu, Metallomics, 2013, 5, 1566
    DOI: 10.1039/C3MT00190C

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