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...
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| Format: | Article |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00230/full |
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| author | Matthias Bochtler Matthias Bochtler Danuta Mizgalska Florian Veillard Magdalena L. Nowak John Houston Paul Veith Eric C. Reynolds Jan Potempa Jan Potempa |
| author_facet | Matthias Bochtler Matthias Bochtler Danuta Mizgalska Florian Veillard Magdalena L. Nowak John Houston Paul Veith Eric C. Reynolds Jan Potempa Jan Potempa |
| author_sort | Matthias Bochtler |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T21:26:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-23T21:26:31Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-3055a5309394476dbe8f1367af6bdfca2022-12-21T17:30:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-03-01910.3389/fmicb.2018.00230313999The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I SubstratesMatthias Bochtler0Matthias Bochtler1Danuta Mizgalska2Florian Veillard3Magdalena L. Nowak4John Houston5Paul Veith6Eric C. Reynolds7Jan Potempa8Jan Potempa9International Institute of Molecular and Cell Biology, Warsaw, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, PolandDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United StatesDepartment of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, PolandDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United StatesOral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, AustraliaOral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, AustraliaDepartment of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, PolandDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United StatesBacteroidetes 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.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00230/fullBacteroidetessignal peptidase Iglutaminyl cyclasepyroglutamatePorphyromonas |
| spellingShingle | Matthias Bochtler Matthias Bochtler Danuta Mizgalska Florian Veillard Magdalena L. Nowak John Houston Paul Veith Eric C. Reynolds Jan Potempa Jan Potempa The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates Frontiers in Microbiology Bacteroidetes signal peptidase I glutaminyl cyclase pyroglutamate Porphyromonas |
| 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 | Bacteroidetes signal peptidase I glutaminyl cyclase pyroglutamate Porphyromonas |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00230/full |
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