Affiliation:
1. Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada
Abstract
Many bacteria possess dynamic filaments called Type IV pili (T4P) that perform diverse functions in colonization and dissemination, including host cell adhesion, DNA uptake, and secretion of protein substrates—exoproteins—from the periplasm to the extracellular space. The
Vibrio cholerae
toxin-coregulated pilus (TCP) and the enterotoxigenic
Escherichia coli
CFA/III pilus each mediates export of a single exoprotein, TcpF and CofJ, respectively. Here, we show that the disordered N-terminal segment of mature TcpF is the export signal (ES) recognized by TCP. Deletion of the ES disrupts secretion and causes TcpF to accumulate in the
V. cholerae
periplasm. The ES alone can mediate export of
Neisseria gonorrhoeae
FbpA by
V. cholerae
in a T4P-dependent manner. The ES is specific for its autologous T4P machinery as CofJ bearing the TcpF ES is exported by
V. cholerae
, whereas TcpF bearing the CofJ ES is not. Specificity is mediated by binding of the ES to TcpB, a minor pilin that primes pilus assembly and forms a trimer at the pilus tip. Finally, the ES is proteolyzed from the mature TcpF protein upon secretion. Together, these results provide a mechanism for delivery of TcpF across the outer membrane and release into the extracellular space.
Funder
Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada
Publisher
Proceedings of the National Academy of Sciences