· D. Verger, E. Miller, H. Remaut, G.
Waksman* and S. Hultgren*
Molecular mechanism of P pilus termination in uropathogenic E. coli
EMBO reports. 7:1228-32. (2006)
P pili are important adhesive fibres
assembled by the conserved chaperone/usher pathway. During pilus assembly, subunits are incorporated into the
growing fibre via the donor-strand exchange mechanism, whereby the chaperone’s beta-strand that complements the incomplete
immunoglobulin-fold of each subunit is displaced by the N-terminal extension of
an incoming subunit in a zip-in-zip-out exchange process that is initiated at
the P5 pocket, an exposed hydrophobic pocket in the subunit’s groove. In vivo, termination of P pilus growth requires a
specialised subunit, PapH. Here,
we demonstrate that PapH is incorporated at the base of the growing pilus where
it is unable to undergo donor strand exchange. This inability is not due to a stronger PapD-PapH
interaction; but instead, the PapH structure reveals that the P5 initiator
pocket is completely lacking, suggesting that PapH terminates pilus growth
because it is lacking the initiation point by which donor strand exchange
proceeds.