ยท H.
Remaut, C. Tang, N.S. Henderson, J.S. Pinkner, T. Wang, S.J. Hultgren*, D.G.
Thanassi*, G. Waksman*, H. Li*.
Fiber Formation Across the Bacterial Outer Membrane by the
Chaperone/Usher Pathway
Cell. 133:640-652 (2008).
*
indicates corresponding author
Gram-negative pathogens commonly exhibit adhesive pili on their surface that mediate specific attachment to the host. A major class of pili is assembled via the chaperone/usher pathway. Here, the structural basis for pilus fiber assembly and secretion performed by the outer membrane assembly platform, the usher, is revealed by the crystal structure of the translocation domain of the P pilus usher PapC and single particle cryo-electron microscopy imaging of the FimD usher bound to a translocating type 1 pilus assembly intermediate. These structures provide molecular snapshots of a twinned pore translocation machinery in action. Unexpectedly, only one pore is used for secretion, while both usher protomers are used for chaperone-subunit complex recruitment. The translocating pore itself comprises 24 beta-strands and is occluded by a folded plug domain, likely gated by a conformationally-constrained beta-hairpin. These structures capture the secretion of a virulence factor across the outer membrane of Gram-negative bacteria.