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Carsten Scavenius

Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity

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Standard

Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity. / Bielecka, Ewa; Scavenius, Carsten; Kantyka, Tomasz; Jusko, Monika; Mizgalska, Danuta; Szmigielski, Borys; Potempa, Barbara; Enghild, Jan Johannes; Prossnitz, Eric; Blom, Anna M; Potempa, Jan.

In: Journal of Biological Chemistry, Vol. 289, 16.10.2014, p. 32481-32487.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Bielecka, E, Scavenius, C, Kantyka, T, Jusko, M, Mizgalska, D, Szmigielski, B, Potempa, B, Enghild, JJ, Prossnitz, E, Blom, AM & Potempa, J 2014, 'Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity', Journal of Biological Chemistry, vol. 289, pp. 32481-32487. https://doi.org/10.1074/jbc.C114.617142

APA

Bielecka, E., Scavenius, C., Kantyka, T., Jusko, M., Mizgalska, D., Szmigielski, B., Potempa, B., Enghild, J. J., Prossnitz, E., Blom, A. M., & Potempa, J. (2014). Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity. Journal of Biological Chemistry, 289, 32481-32487. https://doi.org/10.1074/jbc.C114.617142

CBE

Bielecka E, Scavenius C, Kantyka T, Jusko M, Mizgalska D, Szmigielski B, Potempa B, Enghild JJ, Prossnitz E, Blom AM, Potempa J. 2014. Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity. Journal of Biological Chemistry. 289:32481-32487. https://doi.org/10.1074/jbc.C114.617142

MLA

Vancouver

Bielecka E, Scavenius C, Kantyka T, Jusko M, Mizgalska D, Szmigielski B et al. Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity. Journal of Biological Chemistry. 2014 Oct 16;289:32481-32487. https://doi.org/10.1074/jbc.C114.617142

Author

Bielecka, Ewa ; Scavenius, Carsten ; Kantyka, Tomasz ; Jusko, Monika ; Mizgalska, Danuta ; Szmigielski, Borys ; Potempa, Barbara ; Enghild, Jan Johannes ; Prossnitz, Eric ; Blom, Anna M ; Potempa, Jan. / Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity. In: Journal of Biological Chemistry. 2014 ; Vol. 289. pp. 32481-32487.

Bibtex

@article{4c3bcd601b4a4b8686ab1497ef4e032a,
title = "Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity",
abstract = "Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura 2-AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles (OMVs) naturally shed by P. gingivalis we observed generation of C5a totally citrullinated at the C-terminal Arg74 residue (Arg74Cit). In stark contrast only native C5a was detected after treatment with PPAD-null OMVs. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis.",
author = "Ewa Bielecka and Carsten Scavenius and Tomasz Kantyka and Monika Jusko and Danuta Mizgalska and Borys Szmigielski and Barbara Potempa and Enghild, {Jan Johannes} and Eric Prossnitz and Blom, {Anna M} and Jan Potempa",
note = "Copyright {\textcopyright} 2014, The American Society for Biochemistry and Molecular Biology.",
year = "2014",
month = oct,
day = "16",
doi = "10.1074/jbc.C114.617142",
language = "English",
volume = "289",
pages = "32481--32487",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

}

RIS

TY - JOUR

T1 - Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes C5a activity

AU - Bielecka, Ewa

AU - Scavenius, Carsten

AU - Kantyka, Tomasz

AU - Jusko, Monika

AU - Mizgalska, Danuta

AU - Szmigielski, Borys

AU - Potempa, Barbara

AU - Enghild, Jan Johannes

AU - Prossnitz, Eric

AU - Blom, Anna M

AU - Potempa, Jan

N1 - Copyright © 2014, The American Society for Biochemistry and Molecular Biology.

PY - 2014/10/16

Y1 - 2014/10/16

N2 - Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura 2-AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles (OMVs) naturally shed by P. gingivalis we observed generation of C5a totally citrullinated at the C-terminal Arg74 residue (Arg74Cit). In stark contrast only native C5a was detected after treatment with PPAD-null OMVs. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis.

AB - Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura 2-AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles (OMVs) naturally shed by P. gingivalis we observed generation of C5a totally citrullinated at the C-terminal Arg74 residue (Arg74Cit). In stark contrast only native C5a was detected after treatment with PPAD-null OMVs. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis.

U2 - 10.1074/jbc.C114.617142

DO - 10.1074/jbc.C114.617142

M3 - Journal article

C2 - 25324545

VL - 289

SP - 32481

EP - 32487

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

ER -