A shape-shifting redox foldase contributes to Proteus mirabilis copper resistance.

Autor:	Furlong EJ; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia., Lo AW; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, Queensland 4072, Australia., Kurth F; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia., Premkumar L; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia.; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia., Totsika M; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, Queensland 4072, Australia., Achard MES; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, Queensland 4072, Australia., Halili MA; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia., Heras B; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3068, Australia., Whitten AE; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia., Choudhury HG; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia., Schembri MA; School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, Queensland 4072, Australia., Martin JL; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia.; Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2017 Jul 19; Vol. 8, pp. 16065. Date of Electronic Publication: 2017 Jul 19.
DOI:	10.1038/ncomms16065
Abstrakt:	Copper resistance is a key virulence trait of the uropathogen Proteus mirabilis. Here we show that P. mirabilis ScsC (PmScsC) contributes to this defence mechanism by enabling swarming in the presence of copper. We also demonstrate that PmScsC is a thioredoxin-like disulfide isomerase but, unlike other characterized proteins in this family, it is trimeric. PmScsC trimerization and its active site cysteine are required for wild-type swarming activity in the presence of copper. Moreover, PmScsC exhibits unprecedented motion as a consequence of a shape-shifting motif linking the catalytic and trimerization domains. The linker accesses strand, loop and helical conformations enabling the sampling of an enormous folding landscape by the catalytic domains. Mutation of the shape-shifting motif abolishes disulfide isomerase activity, as does removal of the trimerization domain, showing that both features are essential to foldase function. More broadly, the shape-shifter peptide has the potential for 'plug and play' application in protein engineering.
Databáze:	MEDLINE
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