The F4 fimbrial chaperone FaeE is stable as a monomer that does not require self-capping of its pilin-interactive surfaces.
ABSTRACT Many Gram-negative bacteria use the chaperone-usher pathway to express adhesive surface structures, such as fimbriae, in order to mediate attachment to host cells. Periplasmic chaperones are required to shuttle fimbrial subunits or pilins through the periplasmic space in an assembly-competent form. The chaperones cap the hydrophobic surface of the pilins through a donor-strand complementation mechanism. FaeE is the periplasmic chaperone required for the assembly of the F4 fimbriae of enterotoxigenic Escherichia coli. The FaeE crystal structure shows a dimer formed by interaction between the pilin-binding interfaces of the two monomers. Dimerization and tetramerization have been observed previously in crystal structures of fimbrial chaperones and have been suggested to serve as a self-capping mechanism that protects the pilin-interactive surfaces in solution in the absence of the pilins. However, thermodynamic and biochemical data show that FaeE occurs as a stable monomer in solution. Other lines of evidence indicate that self-capping of the pilin-interactive interfaces is not a mechanism that is conservedly applied by all periplasmic chaperones, but is rather a case-specific solution to cap aggregation-prone surfaces.
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ABSTRACT: Enterotoxigenic Escherichia coli expressing F4 fimbriae are the major cause of porcine colibacillosis and are responsible for significant death and morbidity in neonatal and postweaned piglets. Via the chaperone-usher pathway, F4 fimbriae are assembled into thin, flexible polymers mainly composed of the single-domain adhesin FaeG. The F4 fimbrial system has been labeled eccentric because the F4 pilins show some features distinct from the features of pilins of other chaperone-usher-assembled structures. In particular, FaeG is much larger than other pilins (27 versus approximately 17 kDa), grafting an additional carbohydrate binding domain on the common immunoglobulin-like core. Structural data of FaeG during different stages of the F4 fimbrial biogenesis process, combined with differential scanning calorimetry measurements, confirm the general principles of the donor strand complementation/exchange mechanisms taking place during pilus biogenesis via the chaperone-usher pathway.Journal of Molecular Biology 09/2009; 394(5):957-67. · 3.91 Impact Factor
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ABSTRACT: This review summarizes current knowledge on the structure, function, assembly and biomedical applications of the superfamily of adhesive fimbrial organelles exposed on the surface of Gram-negative pathogens with the classical chaperone/usher machinery. High-resolution three-dimensional (3D) structure studies of the minifibers assembling with the FGL (having a long F1-G1 loop) and FGS (having a short F1-G1 loop) chaperones show that they exploit the same principle of donor-strand complementation for polymerization of subunits. The 3D structure of adhesive subunits bound to host-cell receptors and the final architecture of adhesive fimbrial organelles reveal two functional families of the organelles, respectively, possessing polyadhesive and monoadhesive binding. The FGL and FGS chaperone-assembled polyadhesins are encoded exclusively by the gene clusters of the γ3- and κ-monophyletic groups, respectively, while gene clusters belonging to the γ1-, γ2-, γ4-, and π-fimbrial clades exclusively encode FGS chaperone-assembled monoadhesins. Novel approaches are suggested for a rational design of antimicrobials inhibiting the organelle assembly or inhibiting their binding to host-cell receptors. Vaccines are currently under development based on the recombinant subunits of adhesins.FEMS microbiology reviews 12/2009; 34(3):317-78. · 10.96 Impact Factor