Green E D, Baenziger J U
Department of Pathology, Washington University Medical School, St. Louis, Missouri 63110.
J Biol Chem. 1988 Jan 5;263(1):25-35.
We have elucidated the structures of the anionic asparagine-linked oligosaccharides present on the glycoprotein hormones lutropin (luteinizing hormone), follitropin (follicle-stimulating hormone), and thyrotropin (thyroid-stimulating hormone). Purified hormones, isolated from bovine, ovine, and human pituitaries, were digested with N-glycanase, and the released oligosaccharides were reduced with NaB[3H]4. The 3H-labeled oligosaccharides from each hormone were then fractionated by anion-exchange high performance liquid chromatography (HPLC) into populations differing in the number of sulfate and/or sialic acid moieties. The anionic oligosaccharides were further purified as well as structurally characterized using a variety of preparative and analytical techniques, including HPLC, endo- and exoglycosidase digestions, and lectin affinity chromatography. The sulfated, sialylated, and sulfated/sialylated structures, which together comprised 67-90% of the asparagine-linked oligosaccharides on the pituitary glycoprotein hormones, were highly heterogeneous and displayed hormone- as well as animal species-specific features. The sulfated oligosaccharides consisted of hybrid and complex type oligosaccharides with one or two branches terminating in SO4-4GalNAc beta 1,4. In contrast, the sialylated oligosaccharides consisted of a wide array of differing structures containing two or three peripheral branches as well as one, two, or three sialic acid moieties. A previously uncharacterized dibranched oligosaccharide, bearing one residue each of sulfate and sialic acid, was found on all of the hormones except bovine lutropin. In this study, we describe the purification and detailed structural characterizations of the sulfated, sialylated, and sulfated/sialylated oligosaccharides found on lutropin, follitropin, and thyrotropin from several animal species. In the accompanying paper (Green, E.D., and Baenziger, J.U.(1987) J. Biol. Chem. 262, 36-44) we demonstrate the marked quantitative differences among the pituitary glycoprotein hormones in terms of sulfation, sialylation, and underlying oligosaccharide structures, as well as provide evidence for site-specific synthesis of oligosaccharides on individual hormones.
我们已经阐明了糖蛋白激素促黄体生成素、促卵泡激素和促甲状腺激素上存在的阴离子天冬酰胺连接寡糖的结构。从牛、羊和人垂体中分离出的纯化激素用N-聚糖酶消化,释放出的寡糖用NaB[3H]4还原。然后,通过阴离子交换高效液相色谱(HPLC)将每种激素的3H标记寡糖分离成硫酸根和/或唾液酸部分数量不同的群体。使用包括HPLC、内切和外切糖苷酶消化以及凝集素亲和色谱在内的各种制备和分析技术,对阴离子寡糖进行了进一步纯化和结构表征。硫酸化、唾液酸化和硫酸化/唾液酸化结构共同构成了垂体糖蛋白激素上天冬酰胺连接寡糖的67-9%,它们高度异质,并表现出激素以及动物物种特异性特征。硫酸化寡糖由杂合型和复合型寡糖组成,有一个或两个以SO4-4GalNAcβ1,4结尾的分支。相比之下,唾液酸化寡糖由多种不同结构组成,包含两个或三个外围分支以及一个、两个或三个唾液酸部分。除牛促黄体生成素外所有激素上均发现了一种以前未表征的双分支寡糖,其带有一个硫酸根和一个唾液酸残基。在本研究中,我们描述了从几种动物物种的促黄体生成素、促卵泡激素和促甲状腺激素上发现的硫酸化、唾液酸化和硫酸化/唾液酸化寡糖的纯化和详细结构表征。在随附论文中(格林,E.D.,和贝恩齐格,J.U.(1987年)《生物化学杂志》第262卷,36-44页),我们证明了垂体糖蛋白激素在硫酸化、唾液酸化和潜在寡糖结构方面存在显著的定量差异,并提供了寡糖在各个激素上进行位点特异性合成的证据。