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Lookup NU author(s): Dr Sam Dainty, Dr Rafael Pernil-Garcia, Dr Kevin WaldronORCiD, Dr Andrew Foster, Professor Nigel Robinson
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Copper metallochaperones supply copper to cupro-proteins through copper-mediated protein-protein-interactions and it has been hypothesized that metallochaperones thereby inhibit copper from causing damage en route. Evidence is presented in support of this latter role for cyanobacterial metallochaperone, Atx1. In cyanobacteria Atx1 contributes towards the supply of copper to plastocyanin inside thylakoids but it is shown here that in copper-replete medium, copper can reach plastocyanin without Atx1. Unlike metallochaperone-independent copper-supply to superoxide dismutase in eukaryotes, glutathione is not essential for Atx1-independent supply to plastocyanin: Double mutants missing atx1 and gshB (encoding glutathione synthetase) accumulate the same number of atoms of copper per cell in the plastocyanin pool as wild type. Critically, Delta atx1 Delta gshB are hypersensitive to elevated copper relative to wild type cells and also relative to Delta gshB single mutants with evidence that hypersensitivity arises due to the mislocation of copper to sites for other metals including iron and zinc. The zinc site on the amino-terminal domain (ZiaA(N)) of the P-1-type zinc-transporting ATPase is especially similar to the copper site of the Atx1 target PacS(N), and ZiaA(N) will bind Cu(I) more tightly than zinc. An NMR model of a substituted-ZiaA(N)-Cu(I)-Atx1 heterodimer has been generated making it possible to visualize a juxtaposition of residues surrounding the ZiaA(N) zinc site, including Asp(18), which normally repulse Atx1. Equivalent repulsion between bacterial copper metallochaperones and the amino-terminal regions of P-1-type ATPases for metals other than Cu(I) is conserved, again consistent with a role for copper metallochaperones to withhold copper from binding sites for other metals.
Author(s): Tottey S, Patterson CJ, Banci L, Bertini I, Felli IC, Pavelkova A, Dainty SJ, Pernil R, Waldron KJ, Foster AW, Robinson NJ
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences
Year: 2012
Volume: 109
Issue: 1
Pages: 95-100
Print publication date: 03/01/2012
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: http://dx.doi.org/10.1073/pnas.1117515109
DOI: 10.1073/pnas.1117515109
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