Gemmill T R, Trimble R B
Wadsworth Center C-547, New York State Department of Health, P.O. Box 509, Albany, NY 12201-0509, USA.
Biochim Biophys Acta. 1999 Jan 6;1426(2):227-37. doi: 10.1016/s0304-4165(98)00126-3.
Yeast and most higher eukaryotes utilize an evolutionarily conserved N-linked oligosaccharide biosynthetic pathway that involves the formation of a Glc3Man9GlcNAc2-PP-dolichol lipid-linked precursor, the glycan portion of which is co-translationally transferred in the endoplasmic reticulum (ER) to suitable Asn residues on nascent polypeptides. Subsequently, ER processing glycohydrolases remove the three glucoses and, with the exception of Schizosaccharomyces pombe, a single, specific mannose residue. Processing sugar transferases in the Golgi lead to the formation of core-sized structures (Hex<15GlcNac2) as well as cores with an extended poly-alpha1,6-Man 'backbone' that is derivatized with various carbohydrate side chains in a species-specific manner (Hex50-200GlnNAc2). In some cases these are short alpha1,2-linked Man chains with (Saccharomyces cerevisiae) or without (Pichia pastoris) alpha1,3-Man caps, while in other yeast (S. pombe), the side chains are alpha1,2-linked Gal, some of which are capped with beta-1,3-linked pyruvylated Gal residues. Charged groups are also found in S. cerevisiae and P. pastoris N-glycans in the form of mannose phosphate diesters. Some pathogenic yeast (Candida albicans) add poly-beta1,2-Man extension through a phosphate diester to their N-glycans, which appears involved in virulence. O-Linked glycan synthesis in yeast, unlike in animal cells where it is initiated in the Golgi using nucleotide sugars, begins in the ER by addition of a single mannose from Man-P-dolichol to selected Ser/Thr residues in newly made proteins. Once transported to the Golgi, sugar transferases add one (C. albicans) or more (P. pastoris) alpha1,2-linked mannose that may be capped with one or two alpha1,3-linked mannoses (S. cerevisiae). S. pombe is somewhat unique in that it synthesizes a family of mixed O-glycans with additional alpha1,2-linked Man and alpha1,2- and 1, 3-linked Gal residues.
酵母和大多数高等真核生物利用一种进化上保守的N-连接寡糖生物合成途径,该途径涉及形成Glc3Man9GlcNAc2-PP-多萜醇脂质连接前体,其聚糖部分在内质网(ER)中与新生多肽上合适的天冬酰胺残基共翻译转移。随后,内质网加工糖苷水解酶去除三个葡萄糖,除粟酒裂殖酵母外,还去除一个特定的甘露糖残基。高尔基体中的加工糖基转移酶导致形成核心大小的结构(Hex<15GlcNac2)以及具有延伸的多-α1,6-甘露糖“主链”的核心,该主链以物种特异性方式被各种碳水化合物侧链衍生化(Hex50-200GlnNAc2)。在某些情况下,这些是带有(酿酒酵母)或不带有(巴斯德毕赤酵母)α1,3-甘露糖帽的短α1,2-连接甘露糖链,而在其他酵母(粟酒裂殖酵母)中,侧链是α1,2-连接的半乳糖,其中一些被β-1,3-连接的丙酮酸化半乳糖残基封端。在酿酒酵母和巴斯德毕赤酵母的N-聚糖中也以甘露糖磷酸二酯的形式发现带电基团。一些致病酵母(白色念珠菌)通过磷酸二酯向其N-聚糖添加多-β1,2-甘露糖延伸,这似乎与毒力有关。酵母中的O-连接聚糖合成与动物细胞不同,动物细胞中O-连接聚糖合成在高尔基体中使用核苷酸糖起始,而酵母中O-连接聚糖合成在内质网中通过将来自甘露糖-P-多萜醇的单个甘露糖添加到新合成蛋白质中选定的丝氨酸/苏氨酸残基上开始。一旦转运到高尔基体,糖基转移酶添加一个(白色念珠菌)或更多(巴斯德毕赤酵母)α1,2-连接的甘露糖,这些甘露糖可能被一个或两个α1,3-连接的甘露糖封端(酿酒酵母)。粟酒裂殖酵母有点独特,因为它合成了一系列混合的O-聚糖,带有额外的α1,2-连接甘露糖以及α1,2-和1,3-连接的半乳糖残基。