Hanaoka K, Pritchett T J, Takasaki S, Kochibe N, Sabesan S, Paulson J C, Kobata A
Department of Biochemistry, Institute of Medical Science, University of Tokyo, Japan.
J Biol Chem. 1989 Jun 15;264(17):9842-9.
To investigate the molecular basis of the differential ability of human, equine, and guinea pig alpha 2-macroglobulins to inhibit hemagglutination and infectivity of a human influenza virus, A/Memphis/102/72 (H3N2), the structures of oligosaccharides released from the three glycoproteins by hydrazinolysis were analyzed comparatively. Approximately seven to eight sugar chains were released from each subunit of two potent inhibitors (equine and guinea pig alpha 2-macroglobulins) and a weak inhibitor (human alpha 2-macroglobulin). More than 70% of the oligosaccharides contained sialic acids in all three cases. Structural analysis of these sialo-oligosaccharides revealed that all of the three glycoproteins contain biantennary oligosaccharides with one and two sialic acids as major sugar chains (70-80% of total sugar chains). Four percent of the biantennary oligosaccharides from equine sample, 10% of those from guinea pig, and 24% of those from human contain a fucosylated trimannosyl core. No triantennary oligosaccharide was detected in equine alpha 2-macroglobulin. However, human and guinea pig alpha 2-macroglobulins contain both fucosylated and nonfucosylated triantennary oligosaccharides. All sialic acid residues occur as the Sia alpha 2----6Gal group. The one unique feature of the carbohydrate groups of equine and guinea pig alpha 2-macroglobulins was the presence of 4-O-Ac-Neu5Ac as 30-50% of the total sialic acids, while human alpha 2-macroglobulin contained only Neu 5Ac. However, 4-O-Ac-Neu5Ac is not responsible for the potent inhibition of influenza virus infection and hemagglutination as will be described in the accompanying paper.
为了研究人、马和豚鼠α2-巨球蛋白抑制人甲型流感病毒A/孟菲斯/102/72（H3N2）血凝和感染性的差异能力的分子基础，对通过肼解从这三种糖蛋白释放的寡糖结构进行了比较分析。两种强效抑制剂（马和豚鼠α2-巨球蛋白）和一种弱抑制剂（人α2-巨球蛋白）各自的亚基大约释放出7至8条糖链。在所有三种情况下，超过70%的寡糖含有唾液酸。对这些唾液酸化寡糖的结构分析表明，所有这三种糖蛋白都含有以一个和两个唾液酸作为主要糖链的双天线寡糖（占总糖链的70 - 80%）。马样本中4%的双天线寡糖、豚鼠样本中10%的双天线寡糖以及人样本中24%的双天线寡糖含有岩藻糖基化的三聚甘露糖核心。在马α2-巨球蛋白中未检测到三天线寡糖。然而，人和豚鼠α2-巨球蛋白都含有岩藻糖基化和非岩藻糖基化的三天线寡糖。所有唾液酸残基均以Siaα2----6Gal基团形式存在。马和豚鼠α2-巨球蛋白碳水化合物基团唯一的独特特征是4-O-乙酰神经氨酸占总唾液酸的30 - 50%，而人α2-巨球蛋白仅含有神经氨酸。然而，如随附论文中所述，4-O-乙酰神经氨酸并非流感病毒感染和血凝强效抑制的原因。
