Joint inflammation related citrullination of functional arginines in extracellular proteins

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: Sipilä Kalle H., Ranga Vipin, Rappu Pekka, Mali Markku, Pirilä Laura, Heino Ilona, Jokinen Johanna, Käpylä Jarmo, Johnson Mark S., Heino Jyrki
Publisher: Nature Publishing Group
Place: United Kingdom
Publication year: 2017
Journal: Scientific Reports
Volume number: 7
Start page: 1
End page: 12
eISSN: 2045-2322


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, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction. Citrullination of integrin ligands was selected for further studies since fibronectin R234 in isoDGR was among the most frequently citrullinated arginines in synovial fluid. Assays with synovial fibroblasts and integrin αVβ3 indicated decreased affinity to the enzymatically citrullinated integrin binding sites. To conclude, our data indicate that in inflamed joints extensive citrullination affects the functional arginine residues in extracellular proteins.


Integrin, post-translational modification, protein sequence analysis, protein structure motifs, Rheumatoid arthritis


Last updated on 2020-05-04 at 06:51