Dataset Information

The Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis

ABSTRACT: Porphyrmonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. The colonization of oral epithelial surfaces by P. gingivalis may also lead to the autoimmune disease rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is a post-translational modification of arginine residues, leading to a change in structure and function of the respective protein. This modification is catalysed by peptidylarginine deiminases (PAD). Interestingly, P. gingivalis secretes a citrullinating enzyme, known as P. gingivalis PAD (PPAD), which targets bacterial and human proteins. Since the extent of P. gingivalis protein citrullination by PPAD was not yet known, the present study was aimed at identifying the extracellular proteome and citrullinome of P. gingivalis. To this end, extracellular proteins of two reference strains, two PPAD-deficient mutants and three clinical isolates of P. gingivalis were analysed by mass spectrometry. The results uncovered substantial heterogeneity in the extracellular proteome and citrullinome of P. gingivalis, especially in relation to the extracellular detection of typical cytoplasmic proteins. In contrast, major virulence factors were identified in all investigated isolates although their citrullination was shown to vary. This may be related to post-translational processing of the PPAD enzyme.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Porphyromonas Gingivalis

SUBMITTER: Andreas Otto

LAB HEAD: Andreas Otto

PROVIDER: PXD003444 | Pride | 2018-02-28

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	130609_O2_P1_SG_CG_10.RAW	Raw
	130609_O2_P1_SG_CG_12.RAW	Raw
	130609_O2_P1_SG_CG_2.RAW	Raw
	130609_O2_P1_SG_CG_4.RAW	Raw
	130609_O2_P1_SG_CG_6.RAW	Raw

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Publications

Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis.

Stobernack Tim T Glasner Corinna C Junker Sabryna S Gabarrini Giorgio G de Smit Menke M de Jong Anne A Otto Andreas A Becher Dörte D van Winkelhoff Arie Jan AJ van Dijl Jan Maarten JM

Journal of proteome research 20161019 12

Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is a post-translational modification of arginine residues, leading to a change in structure and function of the respective protein. This modification, which is catalyzed by peptidylarginine deiminases ( ...[more]

PMID: 27712078

Similar Datasets

Project description:Citrullination is a post-translational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations and while the modification has been linked to several diseases including rheumatoid arthritis and cancer, its physiological or pathophysiological roles remain largely unclear. In part this is owing to limitations in available methodology able to robustly enrich, detect and localize the modification. As a result, only few citrullination sites have been identified on human proteins with high confidence. In this study, we mined data from mass spectrometry-based deep proteomic profiling of 30 human tissues to identify citrullination sites on endogenous proteins. Database searching of ~70 million tandem mass spectra yielded ~13,000 candidate spectra which were further triaged by spectrum quality metrics and the detection of the specific neutral loss of isocyanic acid from citrullinated peptides to reduce false positives. Because citrullination is easily confused with deamidation, we synthetised ~2,200 citrullinated and 1,300 deamindated peptides to build a library of reference spectra. This led to the validation of 375 citrullination sites on 209 human proteins. Further analysis showed that >80% of the identified modifications sites were new and for 56% of the proteins, citrullination was detected for the first time. Sequence motif analysis revealed a strong preference for Asp and Gly, residues around the citrullination site. Interestingly, while the modification was detected in 26 human tissues with the highest levels found in brain and lung, citrullination levels did not correlate well with protein expression of the PAD enzymes. Even though the current work represents the largest survey of protein citrullination to date, the modification was mostly detected on high abundance proteins arguing that the development of specific enrichment methods would be required in order to study the full extent of cellular protein citrullination.