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

Area of Science:

• Microbiology
• Structural Biology
• Protein Biochemistry

Background:

• Copper resistance is a critical virulence factor for the uropathogen Proteus mirabilis.
• Understanding the molecular mechanisms of copper resistance is crucial for combating bacterial infections.

Purpose of the Study:

• To investigate the role of P. mirabilis ScsC (PmScsC) in copper resistance.
• To characterize the structure and function of PmScsC, particularly its role in swarming behavior.

Main Methods:

• Biochemical assays to determine disulfide isomerase activity.
• Structural analysis to understand protein trimerization and domain dynamics.
• Mutagenesis studies to assess the importance of specific domains and residues.

Main Results:

• PmScsC enables swarming in P. mirabilis in the presence of copper.
• PmScsC is a trimeric thioredoxin-like disulfide isomerase, distinct from other known proteins in its family.
• Trimerization and the active site cysteine of PmScsC are essential for copper-mediated swarming.
• A unique shape-shifting motif links the catalytic and trimerization domains, facilitating extensive conformational changes and sampling of a large folding landscape.
• Both the shape-shifting motif and trimerization domain are critical for foldase activity.

Conclusions:

• PmScsC is a novel, dynamic disulfide isomerase crucial for Proteus mirabilis virulence through copper resistance and swarming.
• The protein's unique structure and dynamic nature contribute to its essential foldase function.
• The shape-shifter peptide motif holds potential for applications in protein engineering.