Bello-Perez Melissa, Falco Alberto, Medina Regla, Encinar Jose Antonio, Novoa Beatriz, Perez Luis, Estepa Amparo, Coll Julio
Universidad Miguel Hernández, UMH-IBMC, Elche, Spain.
Instituto de Investigaciones Marinas, CSIC, Vigo, España.
Dev Comp Immunol. 2017 Apr;69:33-40. doi: 10.1016/j.dci.2016.12.001. Epub 2016 Dec 10.
Because of the recent discovery of multiple c-reactive protein (crp)-like genes in zebrafish (Danio rerio) with predicted heterogeneous phospholipid-binding amino acid sequences and heterogeneous transcript expression levels in viral survivors and adaptive-deficient mutants, zebrafish constitute an attractive new model for exploring the evolution of these protein's functions, including their possible participation in fish trained immunity. Circulating human CRP belongs to the short pentraxin family of oligomeric proteins that are characteristic of early acute-phase innate responses and is widely used as a clinical inflammation marker. In contrast to pentameric human CRP (pCRP), zebrafish CRPs are trimeric (tCRP); however monomeric CRP (mCRP) conformations may also be generated when associated with cellular membranes as occurs in humans. Compared to human CRP, zebrafish CRP-like proteins show homologous amino acid sequence stretches that are consistent with, although not yet demonstrated, cysteine-dependent redox switches, calcium-binding spots, phosphocholine-binding pockets, C1q-binding domains, regions interacting with immunoglobulin Fc receptors (FcR), unique mCRP epitopes, mCRP binding peptides to cholesterol-enriched rafts, protease target sites, and/or binding sites to monocyte, macrophage, neutrophils, platelets and/or endothelial cells. Amino acid variations among the zebrafish CRP-like multiprotein family and derived isoforms in these stretches suggest that functional heterogeneity best fits the wide variety of aquatic pathogens. As occurs in humans, phospholipid-tagged tCRP-like multiproteins might also influence local inflammation and induce innate immune responses; however, in addition, different zebrafish tCRP-like proteins and/or isoforms might fine tune new still unknown functions. The information reviewed here could be of value for future studies not only to comparative but also medical immunologists and/or fisheries sectors. This review also introduces some novel speculations for future studies.
由于最近在斑马鱼（Danio rerio）中发现了多个c反应蛋白（CRP）样基因，其预测的异质磷脂结合氨基酸序列以及在病毒幸存者和适应性缺陷突变体中的异质转录表达水平，斑马鱼构成了一个有吸引力的新模型，用于探索这些蛋白质功能的进化，包括它们可能参与鱼类训练免疫。循环中的人CRP属于寡聚蛋白的短五聚体家族，是早期急性期先天反应的特征，被广泛用作临床炎症标志物。与五聚体人CRP（pCRP）不同，斑马鱼CRP是三聚体（tCRP）；然而，当与细胞膜结合时，也可能产生单体CRP（mCRP）构象，就像在人类中发生的那样。与人类CRP相比，斑马鱼CRP样蛋白显示出同源氨基酸序列延伸，尽管尚未得到证实，但与半胱氨酸依赖性氧化还原开关、钙结合位点、磷酸胆碱结合口袋、C1q结合域、与免疫球蛋白Fc受体（FcR）相互作用的区域、独特的mCRP表位、mCRP与富含胆固醇的筏的结合肽、蛋白酶靶位点和/或与单核细胞、巨噬细胞、中性粒细胞、血小板和/或内皮细胞的结合位点一致。斑马鱼CRP样多蛋白家族及其在这些延伸中的衍生异构体之间的氨基酸差异表明，功能异质性最适合各种各样的水生病原体。正如在人类中发生的那样，磷脂标记的tCRP样多蛋白也可能影响局部炎症并诱导先天免疫反应；然而，此外，不同的斑马鱼tCRP样蛋白和/或异构体可能会微调新的仍未知的功能。这里回顾的信息不仅对比较免疫学家，而且对医学免疫学家和/或渔业部门的未来研究都可能有价值。本综述还为未来研究引入了一些新的推测。
