The Bacteroidetes Q-rule and glutaminyl cyclase activity increase the stability of extracytoplasmic proteins

mBio. 2023 Oct 31;14(5):e0098023. doi: 10.1128/mbio.00980-23. Epub 2023 Sep 26.

Abstract

Exclusively in the Bacteroidetes phylum, most proteins exported across the inner membrane via the Sec system and released into the periplasm by type I signal peptidase have N-terminal glutamine converted to pyroglutamate. The reaction is catalyzed by the periplasmic enzyme glutaminyl cyclase (QC), which is essential for the growth of Porphyromonas gingivalis and other periodontopathogens. Apparently, pyroglutamyl formation stabilizes extracytoplasmic proteins and/or protects them from proteolytic degradation in the periplasm. Given the role of P. gingivalis as the keystone pathogen in periodontitis, P. gingivalis QC is a promising target for the development of drugs to treat and/or prevent this highly prevalent chronic inflammatory disease leading to tooth loss and associated with severe systemic diseases.

Keywords: Porphyromonas gingivalis; essential protein; periodontitis; posttranslational modification; proteolysis; pyroglutamyl formation.

MeSH terms

  • Aminoacyltransferases* / genetics
  • Aminoacyltransferases* / metabolism
  • Glutamine
  • Humans
  • Periodontitis*
  • Pyrrolidonecarboxylic Acid / metabolism

Substances

  • glutaminyl-peptide cyclotransferase
  • Aminoacyltransferases
  • Pyrrolidonecarboxylic Acid
  • Glutamine