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

Nat Commun. 2017 Jul 19:8:16065. doi: 10.1038/ncomms16065.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Copper*
  • Protein Disulfide-Isomerases / metabolism*
  • Protein Structure, Quaternary
  • Proteus mirabilis / enzymology*
  • Proteus mirabilis / pathogenicity

Substances

  • Copper
  • Protein Disulfide-Isomerases