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Citrullinated proteins in monocyte organelle fractions

ABSTRACT: Citrullinated proteins found in the organelle fractions of monocytes incubated in calcium

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Blood

SUBMITTER: Mekha Thomas

LAB HEAD: Erika Darrah

PROVIDER: PXD044188 | Pride | 2023-10-03

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	071823_Erika_Darrah_Mekha_monocyte_1_5_9.msf	Msf
	C_071823_Erika_Darrah_Mekha_monocyte_1_5_9.pdResult	Other
	OM_Ca_3_donors_PRIDE_SDRF.sdrf.txt	Txt
	Raw_Cit_proteins_monocyte_organelle_Donor_1.raw	Raw
	Raw_Cit_proteins_monocyte_organelle_Donor_2.raw	Raw

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1 - 5 of 8

Publications

An unbiased proteomic analysis of PAD4 in human monocytes: novel substrates, binding partners and subcellular localizations.

Thomas Mekha A MA Kim Seok-Young SY Curran Ashley M AM Smith Barbara B Antiochos Brendan B Na Chan Hyun CH Darrah Erika E

Philosophical transactions of the Royal Society of London. Series B, Biological sciences 20231002 1890

Peptidylarginine deiminase IV (PAD4) post-translationally converts arginine residues in proteins to citrullines and is implicated in playing a central role in the pathogenesis of several diseases. Although PAD4 was historically thought to be a nuclear enzyme, recent evidence has revealed a more complex localization of PAD4 with evidence of additional cytosolic and cell surface localization and activity. However, the mechanisms by which PAD4, which lacks conventional secretory signal sequences, t ...[more]

PMID: 37778379

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Citrullinated glucose-regulated protein 78 is a candidate target for cancer immunotherapy

Project description:In this study we investigate the potential of targeting citrullinated GRP78 for cancer therapy. We select five peptides and show the identification CD4 T cell responses to one citrullinated GRP78 epitope that is restricted through HLA DP*0401 and HLA-DR*0101 alleles. This peptide is detected by mass spectrometry in B16 melanoma grown in vivo and citrulline specific CD4 responses to this epitope mediate efficient therapy of established B16 melanoma tumours in HHDII/DP4 transgenic mouse model. We demonstrate the existence of a repertoire of responses to the citrullinated GRP78 peptide in healthy individuals.

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Confident identification of citrullinated peptides from P gingivalis

Project description:Porphyromonas gingivalis is a key pathogen in the development of chronic periodontitis and has recently been linked to the development of rheumatoid arthritis and Alzheimer’s disease. In this project the outer membrane vesicles (OMV) from Pg have been analyzed using a two-dimensional HFBA-based separation system combined with LC-MS. Three strains from P. gingivalis was analyzed in order to elucidate their citrullinome: wild-type (WT), a mutant with the active site cysteine mutated to alanine (C351A), as well as a knock-out mutant of peptidyl arginine deiminase (ΔPPAD). For optimal and positive identification and validation of citrullinated peptides and proteins, high resolution mass spectrometers and strict MS criteria were utilized. This may have compromised the total number of identified citrullination, but increased the confidence of the validation. A new 2D separation system proved to increase the strength of validation, and along with the use of an in-house build program, Citrullia, we establish a fast and easy semi-automatic (manual) validation of citrullinated peptides. For WT we identified 78 citrullinated proteins having a total of 161 citrullination sites. For C351A a single citrullination site was found and no citrullinations was found for ΔPPAD.

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