Dataset Information

Extracellular citrullination in synovial fluid

ABSTRACT: Citrullination of the proteins found in synovial fluid patient samples

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Synovia

SUBMITTER: Pekka Rappu

LAB HEAD: Jyrki Heino

PROVIDER: PXD004017 | Pride | 2017-08-15

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	140611_PekkaR_K-S10.PTM.msf	Msf
	140611_PekkaR_K-S10.cam.msf	Msf
	140611_PekkaR_K-S10.mgf	Mgf
	140611_PekkaR_K-S10.msf	Msf
	140611_PekkaR_K-S10.raw	Raw

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Publications

Joint inflammation related citrullination of functional arginines in extracellular proteins.

Sipilä Kalle H KH Ranga Vipin V Rappu Pekka P Mali Markku M Pirilä Laura L Heino Ilona I Jokinen Johanna J Käpylä Jarmo J Johnson Mark S MS Heino Jyrki J

Scientific reports 20170815 1

We report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues ...[more]

PMID: 28811641

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.