Intermolecular latency regulates the essential C-terminal signal peptidase and sortase of the <i>Porphyromonas gingivalis</i> type-IX secretion system

Abstract

Significance Selected gram-negative bacteria employ a type-IX secretion system to shuttle virulence proteins with a C-terminal domain (CTD) as a secretion signal across the outer membrane. Upon secretion, the CTD is cleaved and replaced with lipopolysaccharide by PorU, the only known bifunctional signal peptidase and sortase. We discovered that PorU transits between active monomers and latent dimers and determined the structure of the ∼260-kDa dimer. PorU consists of seven domains, including a gingipain-type catalytic domain, which is regulated by a long “latency β-hairpin” that forms an intermolecular β-barrel with the symmetric protomer. Homology modeling followed by in vivo validation revealed that PorU functions as a monomer through a cysteine–histidine catalytic dyad. Thus, dimerization provides an intermolecular mechanism for PorU regulation.