DIFFERENCES IN THE CARBOHYDRATE MOIETIES OF THE COMMON ALPHA-SUBUNITS OF HUMAN CHORIONIC-GONADOTROPIN, LUTEINIZING-HORMONE, FOLLICLE-STIMULATING-HORMONE, AND THYROTROPIN - PRELIMINARY STRUCTURAL INFERENCE FROM DIRECT METHYLATION ANALYSIS

DIFFERENCES IN THE CARBOHYDRATE MOIETIES OF THE COMMON ALPHA-SUBUNITS OF HUMAN CHORIONIC-GONADOTROPIN, LUTEINIZING-HORMONE, FOLLICLE-STIMULATING-HORMONE, AND THYROTROPIN - PRELIMINARY STRUCTURAL INFERENCE FROM DIRECT METHYLATION ANALYSIS
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DOI:
10.1210/endo-119-6-2737
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发表时间:
1986-12-01
期刊:
影响因子:
4.8
通讯作者:
ZOPF, DA
ZOPF, DA
中科院分区:
医学2区
文献类型:
--
作者:
NILSSON, B;ROSEN, SW;ZOPF, DA

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通过直接糖分析和甲基化分析研究了尿hCG和人垂体LH (hLH)、FSH (hFSH)和TSH (hTSH)的组合α-亚基的碳水化合物成分,每个亚基均源自完整激素。该方法提供了与这些糖蛋白相关的复合糖中所含结构元件的完整调查,但没有建立糖序列或糖苷键的异头构型。通过与许多糖蛋白中存在的N-连接寡糖进行类比,数据表明α-亚基与β-亚基组合的碳水化合物具有不同的结构特征。 hCG.α。含有由 NeuAc.alpha.2-3Gal.beta.1- 或 GlcNAc.beta.1-2 Man.alpha.1- 终止的双触角天冬酰胺连接链,并且不含岩藻糖。 hTSH.α。含有与 hCG.alpha 具有相同末端的双触角链。加上末端R-O-4GalNAc和将α1-6连接到N-连接的壳二糖基核心的内部GlcNAc残基的岩藻糖基残基。 hLH.α。可能含有一些高甘露糖链,但主要含有由 NeuAc.alpha.2-3(6)Gal.beta.1-GlcNAc.beta.1-、GalNAc-1-、R''-O-6GlcNAc-1- 和 R''''-O-2Man-1- 以及将 .alpha.1-6 连接至 N-连接壳二糖基的内部 GlcNAc 残基的岩藻糖基残基终止的双触角链核心。 hFSH.α。含有更复杂的结构,可能包括将.beta.1-4连接至3,6-二-O-取代的核心甘露糖基残基的平分GlcNAc残基,以及末端NeuAc.alpha.2-3Gal.beta.1-4(.+-.Fuc.alpha.1-3)GlcNAc-1、Gal.beta.1-4(.+-.Fuc.alpha.1-3)GlcNAc-1-, R''''''-O-GalNAc-1-和GalNAc-1。此外,hFSH.α中存在2,4-二-O-取代的甘露糖。表明它含有三触角链。 R、R''、R'''' 和 R'''''' 基团的身份尚未确定,但最近对糖蛋白激素的研究表明它们可能是硫酸基团。我们的结果证明了在同一器官或什至在同一细胞中产生的几乎相同的多肽激素α-亚基的差异糖基化。
The carbohydrate components of combined .alpha.-subunits of urinary hCG and human pituitary LH (hLH), FSH (hFSH), and TSH (hTSH), each derived from the intact hormone, were studied by direct sugar analysis and methylation analysis. The methods provide a complete survey of the structural elements contained in the complex sugars associated with these glycoproteins, but do not establish the sugar sequences or anomeric configurations of glycosidic bonds. By analogy to N-linked oligosaccharides that occur in many glycoproteins, the data suggest distinct structural features for carbohydrates of .alpha.-subunits combined with .beta.-subunits. hCG.alpha. contains biantennary asparagine-linked chains terminated by either NeuAc.alpha.2-3Gal.beta.1- or GlcNAc.beta.1-2 Man.alpha.1- and lacks fucose. hTSH.alpha. contains biantennary chains with the same termini as hCG.alpha. plus terminal R-O-4GalNAc and a fucosyl residue linked .alpha.1-6 to the inner GlcNAc residue of the N-linked chitobiosyl core. hLH.alpha. may contain some high mannose chains, but primarily contains biantennary chains terminated by NeuAc.alpha.2-3(6)Gal.beta.1-GlcNAc.beta.1-, GalNAc-1-, R''-O-6GlcNAc-1-, and R''''-O-2Man-1- plus a fucosyl residue linked .alpha.1-6 to the inner GlcNAc residue of the N-linked chitobiosyl core. hFSH.alpha. contains more complicated structures that probably include a bisecting GlcNAc residue linked .beta.1-4 to a 3,6-di-O-substituted core mannosyl residue, and terminal NeuAc.alpha.2-3Gal.beta.1-4(.+-.Fuc.alpha.1-3)GlcNAc-1, Gal.beta.1-4(.+-.Fuc.alpha.1-3)GlcNAc-1-, R''''''-O-GalNAc-1-, and GalNAc-1. In addition, the presence of 2,4-di-O-substituted mannose in hFSH.alpha. indicates that it contains triantennary chains. The identities of the R, R'', R'''', and R'''''' groups were not determined, but recent studies of glycoprotein hormones suggest that they may be sulfate groups. Our results demonstrate differential glycosylation of virtually identical polypeptide hormone .alpha.-subunits produced in the same organ or perhaps even in the same cell.