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The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates
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 no...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837995/ https://www.ncbi.nlm.nih.gov/pubmed/29545777 http://dx.doi.org/10.3389/fmicb.2018.00230 |
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author | Bochtler, Matthias Mizgalska, Danuta Veillard, Florian Nowak, Magdalena L. Houston, John Veith, Paul Reynolds, Eric C. Potempa, Jan |
author_facet | Bochtler, Matthias Mizgalska, Danuta Veillard, Florian Nowak, Magdalena L. Houston, John Veith, Paul Reynolds, Eric C. Potempa, Jan |
author_sort | Bochtler, Matthias |
collection | PubMed |
description | 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 Porphyromonas 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. |
format | Online Article Text |
id | pubmed-5837995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58379952018-03-15 The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates Bochtler, Matthias Mizgalska, Danuta Veillard, Florian Nowak, Magdalena L. Houston, John Veith, Paul Reynolds, Eric C. Potempa, Jan Front Microbiol Microbiology 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 Porphyromonas 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. Frontiers Media S.A. 2018-03-01 /pmc/articles/PMC5837995/ /pubmed/29545777 http://dx.doi.org/10.3389/fmicb.2018.00230 Text en Copyright © 2018 Bochtler, Mizgalska, Veillard, Nowak, Houston, Veith, Reynolds and Potempa. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Microbiology Bochtler, Matthias Mizgalska, Danuta Veillard, Florian Nowak, Magdalena L. Houston, John Veith, Paul Reynolds, Eric C. Potempa, Jan The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates |
title | The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates |
title_full | The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates |
title_fullStr | The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates |
title_full_unstemmed | The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates |
title_short | The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates |
title_sort | bacteroidetes q-rule: pyroglutamate in signal peptidase i substrates |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837995/ https://www.ncbi.nlm.nih.gov/pubmed/29545777 http://dx.doi.org/10.3389/fmicb.2018.00230 |
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