Joint inflammation related citrullination of functional arginines in extracellular proteins

Abstract 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. Citrullin...

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Autores principales:	Kalle H. Sipilä, Vipin Ranga, Pekka Rappu, Markku Mali, Laura Pirilä, Ilona Heino, Johanna Jokinen, Jarmo Käpylä, Mark S. Johnson, Jyrki Heino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1499297be840416aa311dd65cde115bb
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spelling	oai:doaj.org-article:1499297be840416aa311dd65cde115bb2021-12-02T16:06:58ZJoint inflammation related citrullination of functional arginines in extracellular proteins10.1038/s41598-017-08597-42045-2322https://doaj.org/article/1499297be840416aa311dd65cde115bb2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08597-4https://doaj.org/toc/2045-2322Abstract 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.Kalle H. SipiläVipin RangaPekka RappuMarkku MaliLaura PiriläIlona HeinoJohanna JokinenJarmo KäpyläMark S. JohnsonJyrki HeinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kalle H. Sipilä Vipin Ranga Pekka Rappu Markku Mali Laura Pirilä Ilona Heino Johanna Jokinen Jarmo Käpylä Mark S. Johnson Jyrki Heino Joint inflammation related citrullination of functional arginines in extracellular proteins
description	Abstract 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.
format	article
author	Kalle H. Sipilä Vipin Ranga Pekka Rappu Markku Mali Laura Pirilä Ilona Heino Johanna Jokinen Jarmo Käpylä Mark S. Johnson Jyrki Heino
author_facet	Kalle H. Sipilä Vipin Ranga Pekka Rappu Markku Mali Laura Pirilä Ilona Heino Johanna Jokinen Jarmo Käpylä Mark S. Johnson Jyrki Heino
author_sort	Kalle H. Sipilä
title	Joint inflammation related citrullination of functional arginines in extracellular proteins
title_short	Joint inflammation related citrullination of functional arginines in extracellular proteins
title_full	Joint inflammation related citrullination of functional arginines in extracellular proteins
title_fullStr	Joint inflammation related citrullination of functional arginines in extracellular proteins
title_full_unstemmed	Joint inflammation related citrullination of functional arginines in extracellular proteins
title_sort	joint inflammation related citrullination of functional arginines in extracellular proteins
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1499297be840416aa311dd65cde115bb
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Joint inflammation related citrullination of functional arginines in extracellular proteins

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