Identification of the interacting regions between an essential component of the type 9 secretion system, PorV, and secreted virulence factors of the oral pathogen, Porphyromonas gingivalis

Summary To better understand how PorV interacts with T9SS substrates and Sov, this project will involve mutagenesis of the inner and outer loop amino acids of PorV followed by characterization of the resulting P. gingivalis mutants to identify specific secretion defects.

Project Details

The type 9 secretion system (T9SS) of the oral Gram-negative pathogen, Porphyromonas gingivalis, is responsible for secreting many CTD-proteins including abundant gingipain proteases that are major virulence factors and contribute to chronic periodontitis in humans. PorV is an outer membrane beta-barrel protein and we have shown it to be an essential component involved in binding to CTD-proteins and interacting with the attachment complex (PorU, PorQ and PorZ) that is responsible for the covalent linkage of CTD-proteins to anionic lipopolysaccharide (A-LPS) which ultimately anchors them to the cell surface. Recently, the structure of an outer membrane component of the T9SS called Sov was determined by cryo-electron microscopy and found to exist as two separate complexes: Sov-Plug and Sov-PorV. We propose that Sov aids PorV in recruiting and translocating the CTD-proteins across the outer membrane in preparation for linkage to A-LPS. To better understand how PorV interacts with T9SS substrates and Sov, this project will involve mutagenesis of the inner and outer loop amino acids of PorV followed by characterization of the resulting P. gingivalis mutants to identify specific secretion defects. Any interaction defects of the mutated PorV protein with either the CTD-proteins and/or Sov will be identified. The student will join a team that are leaders in the field and publishing in high ranking journals.