Vasta Gerardo R, Bianchet Mario A
Department of Microbiology and Immunology, University of Maryland School of Medicine, UMB, and Institute of Marine and Environmental Technology, Baltimore, MD 21202, United States.
Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
BBA Adv. 2025 Jun 14;8:100166. doi: 10.1016/j.bbadva.2025.100166. eCollection 2025.
Among the multiple animal lectin families recognized to date, F-type lectins (FTLs), fucose-binding lectins characterized by an FTL domain (FTLD), constitute the most recent lectin family to be identified and structurally characterized. The structure of the FTL from the European eel revealed a novel jellyroll lectin fold (the "F-type" fold) with unique fucose- and calcium-binding sequence motifs. The FTL lectin family comprises proteins that may exhibit single or multiple FTLD, in combination with structurally and functionally distinct domains, and can form oligomeric associations that display high-avidity multivalent binding. Differences in fine carbohydrate specificity among tandemly arrayed FTLDs present in any FTL polypeptide subunit, together with the expression of multiple FTL isoforms in a single individual supports a broad diversity in ligand recognition. Widely distributed in invertebrates, protochordates, ectothermic vertebrates, birds, and monotreme and marsupial mammals, the FTLD is also present in some bacterial proteins and viruses but absent in placental mammals. The taxonomically broad, and discontinuous distribution of the FTLD, suggests an extensive structural and functional diversification of this lectin family, including horizontal gene transfer in viruses and prokaryotic organisms, together with possible gene loss and/or cooption along the lineages leading to the mammals. FTLs' biological roles range from pathogen recognition in innate immunity to fertilization, cell adhesion and cell aggregation, and as bacterial virulence factors, among others. The specificity of FTLs for fucosylated moieties should provide ample opportunities for novel applications in glycan and cell separation, and innovative diagnostic, preventive, and therapeutic approaches in cancer and infectious disease.
在迄今已识别的多个动物凝集素家族中，F型凝集素（FTLs）是一类以FTL结构域（FTLD）为特征的岩藻糖结合凝集素，是最近才被鉴定并进行结构表征的凝集素家族。欧洲鳗鲡的FTL结构揭示了一种新型的果冻卷凝集素折叠结构（“F型”折叠），具有独特的岩藻糖和钙结合序列基序。FTL凝集素家族包含的蛋白质可能具有单个或多个FTLD，与结构和功能不同的结构域相结合，并能形成显示高亲和力多价结合的寡聚体。任何FTL多肽亚基中串联排列的FTLD之间精细碳水化合物特异性的差异，以及单个个体中多种FTL亚型的表达，支持了配体识别的广泛多样性。FTLD广泛分布于无脊椎动物、原索动物、变温脊椎动物、鸟类、单孔目和有袋类哺乳动物中，也存在于一些细菌蛋白和病毒中，但在胎盘哺乳动物中不存在。FTLD在分类学上分布广泛且不连续，这表明该凝集素家族具有广泛的结构和功能多样化，包括病毒和原核生物中的水平基因转移，以及在导致哺乳动物的谱系中可能的基因丢失和/或基因征用。FTLs的生物学作用范围从先天免疫中的病原体识别到受精、细胞黏附和细胞聚集，以及作为细菌毒力因子等。FTLs对岩藻糖基化部分的特异性应为聚糖和细胞分离的新应用，以及癌症和传染病的创新诊断、预防和治疗方法提供充足的机会。
