Peptidylarginine deiminase and deiminated proteins are detected throughout early halibut ontogeny - Complement components C3 and C4 are post-translationally deiminated in halibut (Hippoglossus hippoglossus L.)

• Published in: Developmental & Comparative Immunology
• Main Authors: Magnadottir, Bergljot, Bragason, Birkir, Bricknell, Ian, Bowden, Timothy, Nicholas, Anthony P., Hristova, Mariya, Guðmundsdóttir, Sigríður, Dodds, Alister W., Lange, Sigrun
• Other Authors: Tilraunastöð í meinafræði að Keldum (HÍ), Institute for Experimental Pathology, Keldur (UI), Háskóli Íslands, University of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier BV 2019
• Subjects: Complement; Halibut; Hippoglossus hippoglossus L; Ontogeny; Pentraxin; Peptidylarginine deiminase; Protein deimination; Lúða; Lífeðlisfræði; Meinafræði; Prótín; Hjalteyri; Willis; Þorlákshöfn; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/1802; https://doi.org/10.1016/j.dci.2018.10.016

Publisher's version (útgefin grein) Post-translational protein deimination is mediated by peptidylarginine deiminases (PADs), which are calcium dependent enzymes conserved throughout phylogeny with physiological and pathophysiological roles. Protein deimination occurs via the conversion of protein arginine into citrulline, leading to structural and functional changes in target proteins. In a continuous series of early halibut development from 37 to 1050° d, PAD, total deiminated proteins and deiminated histone H3 showed variation in temporal and spatial detection in various organs including yolksac, muscle, skin, liver, brain, eye, spinal cord, chondrocytes, heart, intestines, kidney and pancreas throughout early ontogeny. For the first time in any species, deimination of complement components C3 and C4 is shown in halibut serum, indicating a novel mechanism of complement regulation in immune responses and homeostasis. Proteomic analysis of deiminated target proteins in halibut serum further identified complement components C5, C7, C8 C9 and C1 inhibitor, as well as various other immunogenic, metabolic, cytoskeletal and nuclear proteins. Post-translational deimination may facilitate protein moonlighting, an evolutionary conserved phenomenon, allowing one polypeptide chain to carry out various functions to meet functional requirements for diverse roles in immune defences and tissue remodelling. The authors wish to thank Birgir Kristjánsson and the staff at Fiskeldi Eyjafjardar, þorlákshöfn, Iceland, and the staff at Fiskey hf, Hjalteyri, Iceland for providing the fish and sampling facilities. Thanks are due to Sigurður Helgason, Gísli Jónsson and Margrét Jónsdóttir, Keldur, Institute for Experimental Pathology University of Iceland, and to Paul Cook, FRS Marine Laboratory, Aberdeen, Scotland, for preparation of larval samples. Thanks also to Antony Willis, MRC Immunochemistry Unit, Department of Biochemistry, Oxford, for N-terminal amino acid sequence analysis and Michael Deery at the Cambridge Centre for ...