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

Author

Listed:
  • Emily J. Furlong

    (Institute for Molecular Bioscience, University of Queensland)

  • Alvin W. Lo

    (School of Chemistry and Molecular Biosciences, University of Queensland
    Australian Infectious Diseases Research Centre, University of Queensland)

  • Fabian Kurth

    (Institute for Molecular Bioscience, University of Queensland
    Present address: Bristol-Myers Squibb, Arnulfstraße 29, 80636 Munich, Germany)

  • Lakshmanane Premkumar

    (Institute for Molecular Bioscience, University of Queensland
    School of Chemistry and Molecular Biosciences, University of Queensland
    Present address: Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27514, USA)

  • Makrina Totsika

    (School of Chemistry and Molecular Biosciences, University of Queensland
    Australian Infectious Diseases Research Centre, University of Queensland
    Present address: Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia)

  • Maud E. S. Achard

    (School of Chemistry and Molecular Biosciences, University of Queensland
    Australian Infectious Diseases Research Centre, University of Queensland
    Present address: School of Human Movement and Nutrition Sciences, University of Queensland, St Lucia, Queensland 4072, Australia)

  • Maria A. Halili

    (Institute for Molecular Bioscience, University of Queensland)

  • Begoña Heras

    (La Trobe Institute for Molecular Science, La Trobe University)

  • Andrew E. Whitten

    (Institute for Molecular Bioscience, University of Queensland
    Present address: Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organization, Lucas Heights, New South Wales 2234, Australia)

  • Hassanul G. Choudhury

    (Institute for Molecular Bioscience, University of Queensland
    Present address: Cello Health Consulting, Farnham Surrey GU9 7DN, UK)

  • Mark A. Schembri

    (School of Chemistry and Molecular Biosciences, University of Queensland
    Australian Infectious Diseases Research Centre, University of Queensland)

  • Jennifer L. Martin

    (Institute for Molecular Bioscience, University of Queensland
    Griffith Institute for Drug Discovery, Griffith University)

Abstract

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.

Suggested Citation

  • Emily J. Furlong & Alvin W. Lo & Fabian Kurth & Lakshmanane Premkumar & Makrina Totsika & Maud E. S. Achard & Maria A. Halili & Begoña Heras & Andrew E. Whitten & Hassanul G. Choudhury & Mark A. Schem, 2017. "A shape-shifting redox foldase contributes to Proteus mirabilis copper resistance," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16065
    DOI: 10.1038/ncomms16065
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