F-type lectins: Structural and functional aspects, and potential biomedical applications

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 <i>Anguilla anguilla</i> 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.