Structural and functional probing of PorZ, an essential bacterial surface component of the type-IX secretion system of human oral-microbiomic Porphyromonas gingivalis

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DOI

  • Anna M Lasica, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
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  • Theodoros Goulas, Proteolysis Lab, Structural Biology Unit ("María-de-Maeztu¨ Unit of Excellence), Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park, Barcelona, Catalonia, Spain.
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  • Danuta Mizgalska, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Xiaoyan Zhou, Department of Oral Biology, Faculty of Dentistry, University of Sydney, Sydney, NSW 2006, Australia.
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  • Iñaki de Diego, Proteolysis Lab, Structural Biology Unit ("María-de-Maeztu¨ Unit of Excellence), Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park, Barcelona, Catalonia, Spain.
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  • Mirosław Ksiazek, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Mariusz Madej, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Yonghua Guo, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
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  • Tibisay Guevara, Proteolysis Lab, Structural Biology Unit ("María-de-Maeztu¨ Unit of Excellence), Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park, Barcelona, Catalonia, Spain.
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  • Magdalena Nowak, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Barbara Potempa, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
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  • Apoorv Goel, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
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  • Maryta Sztukowska, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
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  • Apurva T Prabhakar, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
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  • Monika Bzowska, Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.
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  • Magdalena Widziolek, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Ida B Thøgersen
  • Jan J Enghild
  • Mary Simonian, Institute of Dental Research, Westmead Centre for Oral Health and Westmead Institute for Medical Research, Sydney, NSW 2145, Australia.
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  • Arkadiusz W Kulczyk, Department of Biological Chemistry and Molecular Pharmacology, Harvard University Medical School, Boston, MA, USA.
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  • Ky-Anh Nguyen, Department of Oral Biology, Faculty of Dentistry, University of Sydney, Sydney, NSW 2006, Australia.
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  • Jan Potempa, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
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  • F Xavier Gomis-Rüth, Proteolysis Lab, Structural Biology Unit ("María-de-Maeztu¨ Unit of Excellence), Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park, Barcelona, Catalonia, Spain.

Porphyromonas gingivalis is a member of the human oral microbiome abundant in dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It employs a newly described type-IX secretion system (T9SS) for secretion of virulence factors. Cargo proteins destined for secretion through T9SS carry a recognition signal in the conserved C-terminal domain (CTD), which is removed by sortase PorU during translocation. Here, we identified a novel component of T9SS, PorZ, which is essential for surface exposure of PorU and posttranslational modification of T9SS cargo proteins. These include maturation of enzyme precursors, CTD removal and attachment of anionic lipopolysaccharide for anchorage in the outer membrane. The crystal structure of PorZ revealed two β-propeller domains and a C-terminal β-sandwich domain, which conforms to the canonical CTD architecture. We further documented that PorZ is itself transported to the cell surface via T9SS as a full-length protein with its CTD intact, independently of the presence or activity of PorU. Taken together, our results shed light on the architecture and possible function of a novel component of the T9SS. Knowledge of how T9SS operates will contribute to our understanding of protein secretion as part of host-microbiome interactions by dysbiotic members of the human oral cavity.

Original languageEnglish
Article number37708
JournalScientific Reports
Volume6
Number of pages22
ISSN2045-2322
DOIs
Publication statusPublished - 24 Nov 2016

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