Magnadóttir Bergljót, Hayes Polly, Hristova Mariya, Bragason Birkir Thor, Nicholas Anthony P, Dodds Alister W, Guðmundsdóttir Sigríður, Lange Sigrun
Institute for Experimental Pathology, University of Iceland, Keldur v. Vesturlandsveg, 112 Reykjavik, Iceland.
Department of Biomedical Sciences, University of Westminster, London, W1W 6UW, UK.
Dev Comp Immunol. 2018 Oct;87:157-170. doi: 10.1016/j.dci.2018.06.006. Epub 2018 Jun 14.
Peptidylarginine deiminases (PADs) are calcium dependent enzymes with physiological and pathophysiological roles conserved throughout phylogeny. PADs promote post-translational deimination of protein arginine to citrulline, altering the structure and function of target proteins. Deiminated proteins were detected in the early developmental stages of cod from 11 days post fertilisation to 70 days post hatching. Deiminated proteins were present in mucosal surfaces and in liver, pancreas, spleen, gut, muscle, brain and eye during early cod larval development. Deiminated protein targets identified in skin mucosa included nuclear histones; cytoskeletal proteins such as tubulin and beta-actin; metabolic and immune related proteins such as galectin, mannan-binding lectin, toll-like receptor, kininogen, Beta2-microglobulin, aldehyde dehydrogenase, bloodthirsty and preproapolipoprotein A-I. Deiminated histone H3, a marker for anti-pathogenic neutrophil extracellular traps, was particularly elevated in mucosal tissues in immunostimulated cod larvae. PAD-mediated protein deimination may facilitate protein moonlighting, allowing the same protein to exhibit a range of biological functions, in tissue remodelling and mucosal immune defences in teleost ontogeny.
肽基精氨酸脱亚氨酶（PADs）是钙依赖性酶，在整个系统发育过程中具有保守的生理和病理生理作用。PADs促进蛋白质精氨酸的翻译后脱亚氨作用生成瓜氨酸，从而改变靶蛋白的结构和功能。在鳕鱼受精后11天至孵化后70天的早期发育阶段检测到了脱亚氨蛋白。在鳕鱼幼体早期发育过程中，脱亚氨蛋白存在于黏膜表面以及肝脏、胰腺、脾脏、肠道、肌肉、大脑和眼睛中。在皮肤黏膜中鉴定出的脱亚氨蛋白靶标包括核组蛋白；细胞骨架蛋白，如微管蛋白和β-肌动蛋白；代谢和免疫相关蛋白，如半乳糖凝集素、甘露聚糖结合凝集素、Toll样受体、激肽原、β2-微球蛋白、醛脱氢酶、嗜血蛋白和前载脂蛋白A-I。脱亚氨组蛋白H3是抗病原中性粒细胞胞外陷阱的标志物，在免疫刺激的鳕鱼幼体的黏膜组织中尤其升高。PAD介导的蛋白质脱亚氨作用可能有助于蛋白质的兼职功能，使同一蛋白质在硬骨鱼个体发育中的组织重塑和黏膜免疫防御中发挥一系列生物学功能。
