Abstract
Pilin proteins assemble into Type IV pili (T4P), surface-displayed bacterial filaments with virulence functions including motility, attachment, transformation, immune escape, and colony formation. However, challenges in crystallizing full-length fiber-forming and membrane protein pilins leave unanswered questions regarding pilin structures, assembly, functions, and vaccine potential. Here we report pilin structures of full-length DnFimA from the sheep pathogen Dichelobacter nodosus and FtPilE from the human pathogen Francisella tularensis at 2.3 and 1 Å resolution, respectively. The DnFimA structure reveals an extended kinked N-terminal α-helix, an unusual centrally located disulfide, conserved subdomains, and assembled epitopes informing serogroup vaccines. An interaction between the conserved Glu-5 carboxyl oxygen and the N-terminal amine of an adjacent subunit in the crystallographic dimer is consistent with the hypothesis of a salt bridge between these groups driving T4P assembly. The FtPilE structure identifies an authentic Type IV pilin and provides a framework for understanding the role of T4P in F. tularensis virulence. Combined results define a unified pilin architecture, specialized subdomain roles in pilus assembly and function, and potential therapeutic targets.
Highlights
The Type IV pili are bacterial pilin polymers with multiple functions in pathogenesis
Individual helices are not resolved in the GC pilus electron microscopy (EM) reconstruction, the known helical symmetry places the conserved Glu-5 of each pilin subunit at the same level in the filament as the positively charged N terminus of its neighboring subunit, allowing these charged residues to neutralize each other in the otherwise hydrophobic core of the filament
That this charge pair interaction is seen in the crystallographic dimer in nonphysiological conditions suggests a specific attraction and is consistent with our hypothesis that an analogous N1–Glu-5 interaction acts in filament assembly [6]
Summary
The Type IV pili are bacterial pilin polymers with multiple functions in pathogenesis. Pilin proteins assemble into Type IV pili (T4P), surface-displayed bacterial filaments with virulence functions including motility, attachment, transformation, immune escape, and colony formation. Combined results define a unified pilin architecture, specialized subdomain roles in pilus assembly and function, and potential therapeutic targets. T4P mediate multiple diverse functions, including adhesion, microcolony formation, twitching motility, and natural transformation They are assembled from thousands of copies of the major pilin subunit, which exist as inner membrane-anchored proteins prior to pilus assembly [3]. Further pilin structure characterizations and their implications for T4P structurefunction relationships are critical for improved understanding
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