Lehmann Friederike, Kelm Sørge, Dietz Frank, von Itzstein Mark, Tiralongo Joe
Institute for Glycomics, Gold Coast Campus, Griffith University, QLD, 4222, Australia.
Glycoconj J. 2008 May;25(4):323-34. doi: 10.1007/s10719-007-9078-4. Epub 2007 Nov 1.
Sialyltransferases are a family of enzymes catalyzing the transfer of sialic acid residues to terminal non-reducing positions of oligosaccharide chains of glycoproteins and glycolipids. Although expression of sialic acid is well documented in animals of the deuterostomian lineage, sialyltransferases have been predominantly described for relatively recent vertebrate lineages such as birds and mammals. This study outlines the characterization of the only sialyltransferase gene found in the tunicate Ciona intestinalis, the first such report of a non-vertebrate deuterostomian sialyltransferase, which has been discussed as a possible orthologue of the common ancestor of galactose alpha2,3-sialyltransferases. We also report for the first time the characterization of a ST3Gal II gene from the bony fish Takifugu rubripes. We demonstrate that both genes encode functional alpha2,3-sialyltransferases that are structurally and functionally related to the ST3Gal family of mammalian sialyltransferases. However, characterization of the recombinant, purified forms of both enzymes reveal novel acceptor substrate specificities, with sialylation of the disaccharide Galbeta1-3GalNAc and asialofetuin, but not GM1 or GD1b observed. This is in contrast to the mammalian ST3Gal II that predominantly sialylates gangliosides. Taken together the ceramide binding/recognition site previously proposed for the mouse ST3Gal II might represent a unique feature of mammalian ST3Gal II that is missing in the evolutionary more distant fish and tunicate species reported here. This suggests that during the evolution of the ST3Gal II, probably following the separation of the teleosts, a significant shift in substrate specificity enabling the sialylation of gangliosides took place.
唾液酸转移酶是一类催化唾液酸残基转移至糖蛋白和糖脂寡糖链末端非还原位置的酶。尽管在后口动物谱系的动物中唾液酸的表达已有充分记录,但唾液酸转移酶主要在鸟类和哺乳动物等相对较新的脊椎动物谱系中被描述。本研究概述了在被囊动物玻璃海鞘中发现的唯一唾液酸转移酶基因的特征,这是首次报道非脊椎后口动物的唾液酸转移酶,该酶被认为可能是半乳糖α2,3 - 唾液酸转移酶共同祖先的直系同源物。我们还首次报道了来自硬骨鱼红鳍东方鲀的ST3Gal II基因的特征。我们证明这两个基因都编码功能性的α2,3 - 唾液酸转移酶,它们在结构和功能上与哺乳动物唾液酸转移酶的ST3Gal家族相关。然而,对这两种酶的重组纯化形式的表征揭示了新的受体底物特异性,观察到二糖Galβ1 - 3GalNAc和去唾液酸胎球蛋白被唾液酸化,但GM1或GD1b未被唾液酸化。这与主要使神经节苷脂唾液酸化的哺乳动物ST3Gal II形成对比。综合来看,先前为小鼠ST3Gal II提出的神经酰胺结合/识别位点可能代表了哺乳动物ST3Gal II的独特特征,而在此报道的进化上距离较远的鱼类和被囊动物物种中则不存在。这表明在ST3Gal II的进化过程中,可能在硬骨鱼分化之后,底物特异性发生了显著转变,使得神经节苷脂能够被唾液酸化。