C5a peptidases are surface-associated serine proteases that enable pathogenic streptococci to evade innate immunity by degrading neutrophil chemoattractants. These enzymes are canonically anchored to the bacterial cell wall via an LPXTG motif and have only been characterized as monomers. Here, we report the cryo-EM structure of an unexpected supramolecular assembly from Streptococcus sanguinis, in which an Streptococcal C5a peptidase-like (ScpH) oligomerizes into an extended filament scaffolded on extracellular DNA (eDNA). The 3.1 A resolution structure reveals that this protease forms interlocked dimers through reciprocal contacts between the Ig and protease-Fn domains, and that these dimers propagate into a double-rowed filament via three additional inter-protomer interfaces. The central eDNA strand is engaged by an electropositive cleft formed by the C-terminal FIVAR3 domain and the DNA-binding tail, which replace the LPXTG anchor found in characterized orthologs. AlphaFold3 predictions indicate that both dimerization and eDNA binding are conserved across a subfamily of streptococcal species that are prominent oral colonizers and eDNA producers. The catalytic triad is structurally intact and a co-purified peptide occupies the active site, although proteolytic activity remains to be demonstrated. This structure reveals a previously unknown mechanism of biofilm functionalization in which a putative immune evasion protease is assembled directly onto eDNA, transforming a passive structural component of the biofilm matrix into a potential catalytic platform.
Fronzes, R., Anger, R., Pieulle, L., Vallart, A., Baudeau, L., Pelicic, V.
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