Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Nov 20;378(1890):20220244.
doi: 10.1098/rstb.2022.0244. Epub 2023 Oct 2.

Citrullination of matrisomal proteins in health and diseases

Mohammad Aslam Saifi  1   2 , I-Cheng Ho  1   2
Affiliations
Review

Citrullination of matrisomal proteins in health and diseases

Mohammad Aslam Saifi et al. Philos Trans R Soc Lond B Biol Sci. .

Abstract

Proteins once translated are subjected to post-translational modifications (PTMs) that can critically modify their characteristics. Citrullination is a unique type of PTM that is catalysed by peptidylarginine deiminase (PAD) enzymes, which regulate a multitude of physiological functions such as apoptosis, gene expression and immune response by altering the structure and function of cellular proteins. However, emerging data have unravelled compelling evidence to support that PAD-mediated citrullination is not exclusive to cellular proteins; rather citrullination of extracellular matrix (ECM) proteins also plays a major contributing role in various physiological/pathological conditions. Here, we discuss putative mechanisms for citrullination-induced alterations in the function of ECM proteins. Further, we put emphasis on influential roles of ECM citrullination in various pathological scenarios to underscore the clinical potential of its manipulation in human diseases. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.

Keywords: citrullination; deiminase; deimination; extracellular matrix; post-translational modification.

PubMed Disclaimer

Conflict of interest statement

We declare we have no competing interests.

Figures

Figure 1.
Figure 1.
A schematic diagram of protein citrullination.
Figure 2.
Figure 2.
A schematic diagram depicting that citrullination interferes with the interaction between ECM proteins and integrins.
Figure 3.
Figure 3.
Schematic diagrams depicting that citrullination modulates the remodelling of ECM composition by abolishing cleavage sites of arginine-directed proteases in ECM proteins (a) and regulating the activity of proteases in cis (the left model in (b)) or in trans (the right model in (b)).
Figure 4.
Figure 4.
A schematic diagram showing that citrullination inhibits not only the release of active TGF-β through interfering with the interaction between LAP and integrins but also the binding of active TGF-β to TGF-β-RII.
Figure 5.
Figure 5.
A schematic diagram showing citrullination of fibrinogen/fibrin alters TLR4 signaling.
See this image and copyright information in PMC

References

    1. Shao X, Taha IN, Clauser KR, Gao Y, Naba A. 2020. MatrisomeDB: the ECM-protein knowledge database. Nucleic Acids Res. 48, D1136-D1144. (10.1093/nar/gkz849) - DOI - PMC - PubMed
    1. Naba A, Clauser KR, Ding H, Whittaker CA, Carr SA, Hynes RO. 2016. The extracellular matrix: tools and insights for the ‘omics’ era. Matrix. Biol. 49, 10-24. (10.1016/j.matbio.2015.06.003) - DOI - PMC - PubMed
    1. Mouw JK, Ou G, Weaver VM. 2014. Extracellular matrix assembly: a multiscale deconstruction. Nat. Rev. Mol. Cell Biol. 15, 771-785. (10.1038/nrm3902) - DOI - PMC - PubMed
    1. Karamanos NK, et al. 2021. A guide to the composition and functions of the extracellular matrix. FEBS J. 288, 6850-6912. (10.1111/febs.15776) - DOI - PubMed
    1. Verheul MK, Van Veelen PA, Van Delft MAM, De Ru A, Janssen GMC, Rispens T, Toes REM, Trouw LA. 2018. Pitfalls in the detection of citrullination and carbamylation. Autoimmun Rev. 17, 136-141. (10.1016/j.autrev.2017.11.017) - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources