Protein citrullination: inhibition, identification and insertion

Protein citrullination: inhibition, identification and insertion

Protein citrullination is a post-translational modification (PTM) that is catalysed by the protein arginine deiminase (PAD) family of enzymes. This PTM involves the transformation of an arginine residue into citrulline. Protein citrullination is associated with several physiological processes, inclu...

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Bibliographic Details
Published in:Philosophical transactions of the Royal Society of London. Series B. Biological sciences 2023-11, Vol.378 (1890), p.20220240-20220240
Main Authors: Barasa, Leonard, Thompson, Paul R
Format: Article
Language:eng
Subjects:
Arthritis, Rheumatoid - genetics
Arthritis, Rheumatoid - metabolism
Citrullination
Citrulline - genetics
Citrulline - metabolism
Epigenesis, Genetic
Humans
Protein Processing, Post-Translational
Protein-Arginine Deiminases - genetics
Protein-Arginine Deiminases - metabolism
Proteins - genetics
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Summary:Protein citrullination is a post-translational modification (PTM) that is catalysed by the protein arginine deiminase (PAD) family of enzymes. This PTM involves the transformation of an arginine residue into citrulline. Protein citrullination is associated with several physiological processes, including the epigenetic regulation of gene expression, neutrophil extracellular trap formation and DNA damage-induced apoptosis. Aberrant protein citrullination is relevant to several autoimmune and neurodegenerative diseases and certain forms of cancer. PAD inhibitors have shown remarkable efficacy in a range of diseases including rheumatoid arthritis (RA), lupus, atherosclerosis and ulcerative colitis. In RA, anti-citrullinated protein antibodies can be detected prior to disease onset and are thus a valuable diagnostic tool for RA. Notably, citrullinated proteins may serve more generally as biomarkers of specific disease states; however, the identification of citrullinated protein residues remains challenging owing to the small 1 Da mass change that occurs upon citrullination. Herein, we highlight the progress made so far in the development of pan-PAD and isozyme selective inhibitors as well as the identification of citrullinated proteins and the site-specific incorporation of citrulline into proteins. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.
ISSN:0962-8436
1471-2970