Joint inflammation related citrullination of functional arginines in extracellular proteins

Sipilä Kalle H., Vipin Ranga, Rappu Pekka, Mali Markku, Pirilä Laura, Heino Ilona, Jokinen Johanna, Käpylä Jarmo, Mark S Johnson, Heino Jyrki

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

11 Citeringar (Scopus)
4 Nedladdningar (Pure)

Sammanfattning

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.

OriginalspråkOdefinierat/okänt
Sidor (från-till)1–12
TidskriftScientific Reports
Volym7
DOI
StatusPublicerad - 2017
MoE-publikationstypA1 Tidskriftsartikel-refererad

Nyckelord

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

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