Laursen S B, Hedemand J E, Thiel S, Willis A C, Skriver E, Madsen P S, Jensenius J C
Department of Medical Microbiology and Immunology, Aarhus University, Denmark.
Glycobiology. 1995 Sep;5(6):553-61. doi: 10.1093/glycob/5.6.553.
A chicken serum lectin was isolated by affinity chromatography on TSK-75 beads derivatized with the monosaccharide N-acetyl-D-mannosamine (ManNAc). Serum was applied to the column in a Ca(2+)-containing buffer and proteins were eluted with EDTA. After recalcification, the eluate was passed through a new ManNAc-derivatized column. Bound proteins were eluted with 50 mM ManNAc. Anti-carbohydrate antibodies present in the eluate were removed by passage through a rabbit anti-chicken immunoglobulin derivatized column, and the lectin was further purified by ion-exchange chromatography and gel-permeation chromatography. The purified chicken lectin shows an overall structure similar to mammalian mannan-binding protein (MBP). SDS-PAGE revealed two polypeptides of M(r) 33 and 34 kDa (reduced) with identical sequence for the first 30 NH2-terminal residues. The NH2-terminal sequence shows 43% identity with the human MBP. Like mammalian MBP, the polypeptides of the chicken lectin are degraded by treatment with collagenase. Residues 26-30 (G-L-P(OH)-G-D) are likely to represent the beginning of the collagenous region. Mobilities on SDS-PAGE of the COOH-terminal collagenase-resistant fragment under reduced and non-reduced conditions indicate the presence of intrachain disulphide bonds, as are also found in mammalian MBP. Gel chromatography showed an intact mol. wt of 750 kDa. Binding of the chicken MBP to mannan was inhibited by monosaccharides in the following order of potency: ManNAc > L-fucose > mannose > N-acetylglucosamine. Other monosaccharides inhibited poorly or not at all. Chicken MBP, bound to mannan, activated the classical complement pathway in human serum. Electron micrographs show structures and dimensions resembling human MBP. Overall, the results show that the purified lectin is the chicken homologue to mammalian MBP and indicate the presence of a MBP-like clearance system outside mammals.
通过在经单糖N-乙酰-D-甘露糖胺(ManNAc)衍生化的TSK-75磁珠上进行亲和层析,分离出一种鸡血清凝集素。血清在含Ca(2+)的缓冲液中加到柱上,蛋白质用EDTA洗脱。重新加入钙离子后,洗脱液通过一根新的ManNAc衍生化柱。结合的蛋白质用50 mM ManNAc洗脱。洗脱液中存在的抗碳水化合物抗体通过一根经兔抗鸡免疫球蛋白衍生化的柱除去,凝集素通过离子交换层析和凝胶渗透层析进一步纯化。纯化的鸡凝集素显示出与哺乳动物甘露聚糖结合蛋白(MBP)相似的整体结构。SDS-PAGE显示出两条分子量分别为33 kDa和34 kDa(还原态)的多肽,其前30个NH2末端残基序列相同。NH2末端序列与人MBP有43%的同源性。与哺乳动物MBP一样,鸡凝集素的多肽经胶原酶处理后会被降解。第26 - 30位残基(G-L-P(OH)-G-D)可能代表胶原区的起始。在还原和非还原条件下,COOH末端抗胶原酶片段在SDS-PAGE上的迁移率表明存在链内二硫键,这在哺乳动物MBP中也有发现。凝胶层析显示完整分子量为750 kDa。鸡MBP与甘露聚糖的结合被单糖按以下效力顺序抑制:ManNAc > L-岩藻糖 > 甘露糖 > N-乙酰葡糖胺。其他单糖抑制作用较弱或根本没有抑制作用。与甘露聚糖结合的鸡MBP激活人血清中的经典补体途径。电子显微镜照片显示出与人类MBP相似的结构和尺寸。总体而言,结果表明纯化的凝集素是哺乳动物MBP的鸡同源物,并表明在哺乳动物之外存在类似MBP的清除系统。