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

The chaperone/usher (CU) pathway is responsible for biogenesis of 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. Assembly and secretion of pili by the CU pathway requires a dedicated periplasmic chaperone and a multidomain 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 served as a central switch controlling usher activation. In addition, 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.
 [1] ;  [2] ;  [1] ;  [1] ;  [2] ;  [3] ;  [1]
  1. Stony Brook Univ., Stony Brook, NY (United States)
  2. Stony Brook Univ., Stony Brook, NY (United States); Brookhaven National Lab. (BNL), Upton, NY (United States)
  3. Washington Univ., St. Louis, MO (United States)
Publication Date:
Report Number(s):
Journal ID: ISSN 1545-9993; 600301010
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 22; Journal Issue: 7; Journal ID: ISSN 1545-9993
Nature Publishing Group
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
National Institute of Health
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; membrane proteins; pathogens; protein translocation
OSTI Identifier: