The pilus usher controls protein interactions via domain masking and is functional as an oligomer

Nat Struct Mol Biol. 2015 Jul;22(7):540-6. doi: 10.1038/nsmb.3044. Epub 2015 Jun 8.


The chaperone-usher (CU) pathway assembles organelles termed pili or fimbriae in Gram-negative bacteria. Type 1 pili expressed by uropathogenic Escherichia coli are prototypical structures assembled by the CU pathway. Biogenesis of pili by the CU pathway requires a periplasmic chaperone and an outer-membrane protein termed the usher (FimD). We show that the FimD C-terminal domains provide the high-affinity substrate-binding site but that these domains are masked in the resting usher. Domain masking requires the FimD plug domain, which serves as a switch controlling usher activation. We demonstrate that usher molecules can act in trans for pilus biogenesis, providing conclusive evidence for a functional usher oligomer. These results reveal mechanisms by which molecular machines such as the usher regulate and harness protein-protein interactions and suggest that ushers may interact in a cooperative manner during pilus assembly in bacteria.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Escherichia coli / chemistry
  • Escherichia coli / cytology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Fimbriae Proteins / chemistry*
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism*
  • Gene Deletion
  • Models, Molecular
  • Protein Interaction Maps*
  • Protein Structure, Tertiary


  • Escherichia coli Proteins
  • fimD protein, E coli
  • Fimbriae Proteins