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Front. Microbiol. | doi: 10.3389/fmicb.2018.00230

The Bacteroidetes Q-rule: Pyroglutamate in signal peptidase I substrates

 Matthias Bochtler1, 2*, Danuta Mizgalska3, Florian Veillard4, Magdalena L. Nowak3, John Houston4, Paul Veith5,  Eric C. Reynolds5 and Jan Potempa3, 4
  • 1International Institute of Molecular and Cell Biology in Warsaw (IIMCB), Poland
  • 2Institute of Biochemistry and Biophysics (PAN), Poland
  • 3Jagiellonian University, Poland
  • 4University of Louisville, United States
  • 5University of Melbourne, Australia

Bacteroidetes feature prominently in the human microbiome, as major colonizers of the gut and clinically relevant pathogens elsewhere. Here, we reveal a new Bacteroidetes specific feature in the otherwise widely conserved Sec/SPI (Sec translocase/signal peptidase I) pathway. In Bacteroidetes, but not the entire FCB group or related phyla, signal peptide cleavage exposes N-terminal glutamine residues in most SPI substrates. Reanalysis of published mass spectrometry data for five Bacteroidetes species shows that the newly exposed glutamines are cyclized to pyroglutamate (also termed 5-oxoproline) residues. Using the dental pathogen P. gingivalis as a model, we identify the PG2157 (also called PG_RS09565, Q7MT37) as the glutaminyl cyclase in this species, and map the catalytic activity to the periplasmic face of the inner membrane. Genetic manipulations that alter the glutamine residue immediately after the signal peptide in the pre-pro-forms of the gingipains affect the extracellular proteolytic activity of RgpA, but not RgpB and Kgp. Glutamine statistics, mass spectrometry data and the mutagenesis results show that the N-terminal glutamine residues or their pyroglutamate cyclization products do not act as generic sorting signals.

Keywords: Bacteroidetes, Signal peptidase I, Glutaminyl cyclase, Pyroglutamate, Porphyromonas

Received: 25 Sep 2017; Accepted: 30 Jan 2018.

Edited by:

Haiwei Luo, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong

Reviewed by:

Hua Xie, Meharry Medical College, United States
Peng Xing, Nanjing Institute of Geography and Limnology (CAS), China
Varun Jaiswal, Shoolini University of Biotechnology and Management Sciences, India  

Copyright: © 2018 Bochtler, Mizgalska, Veillard, Nowak, Houston, Veith, Reynolds and Potempa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Matthias Bochtler, International Institute of Molecular and Cell Biology in Warsaw (IIMCB), Trojedena 4, Warsaw, 02-109, Poland,