Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental (IBYME - CONICET), Buenos Aires, Argentina.
Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro Paladini (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Biochem Soc Trans. 2020 Jun 30;48(3):1255-1268. doi: 10.1042/BST20200311.
Galectin-8 (Gal-8) is a tandem-repeat type galectin with affinity for β-galactosides, bearing two carbohydrate recognition domains (CRD) connected by a linker peptide. The N- and C-terminal domains (Gal-8N and Gal-8C) share 35% homology, and their glycan ligand specificity is notably dissimilar: while Gal-8N shows strong affinity for α(2-3)-sialylated oligosaccharides, Gal-8C has higher affinity for non-sialylated oligosaccharides, including poly-N-acetyllactosamine and/ or A and B blood group structures. Particularly relevant for understanding the biological role of this lectin, full-length Gal-8 can bind cell surface glycoconjugates with broader affinity than the isolated Gal-8N and Gal-8C domains, a trait also described for other tandem-repeat galectins. Herein, we aim to discuss the potential use of separate CRDs in modelling tandem-repeat galectin-8 and its biological functions. For this purpose, we will cover several aspects of the structure-function relationship of this protein including crystallographic structures, glycan specificity, cell function and biological roles, with the ultimate goal of understanding the potential role of each CRD in predicting full-length Gal-8 involvement in relevant biological processes.
半乳糖凝集素-8（Gal-8）是一种具有β-半乳糖苷亲和力的串联重复型半乳糖凝集素，具有两个糖识别结构域（CRD），由连接肽连接。N 端和 C 端结构域（Gal-8N 和 Gal-8C）具有 35%的同源性，其糖配体特异性明显不同：Gal-8N 对α（2-3）-唾液酸化寡糖具有很强的亲和力，而 Gal-8C 对非唾液酸化寡糖具有更高的亲和力，包括多 N-乙酰乳糖胺和/或 A 和 B 血型结构。对于理解这种凝集素的生物学作用特别重要的是，全长 Gal-8 可以与细胞表面糖缀合物结合，其亲和力比分离的 Gal-8N 和 Gal-8C 结构域更广，这一特性也在其他串联重复半乳糖凝集素中得到描述。在此，我们旨在讨论在建模串联重复半乳糖凝集素-8及其生物学功能中单独 CRD 的潜在用途。为此，我们将涵盖该蛋白质结构-功能关系的几个方面，包括晶体结构、糖特异性、细胞功能和生物学作用，最终目的是了解每个 CRD 在预测全长 Gal-8 参与相关生物学过程中的潜在作用。
