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克氏锥虫糖基磷脂酰肌醇锚定的黏蛋白样唾液酸受体的脂质结构在寄生虫从无鞭毛体分化为感染性循环后期锥鞭毛体形式的过程中发生变化。

The lipid structure of the glycosylphosphatidylinositol-anchored mucin-like sialic acid acceptors of Trypanosoma cruzi changes during parasite differentiation from epimastigotes to infective metacyclic trypomastigote forms.

作者信息

Serrano A A, Schenkman S, Yoshida N, Mehlert A, Richardson J M, Ferguson M A

机构信息

Departmento de Microbiologia, Immunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Brazil.

出版信息

J Biol Chem. 1995 Nov 10;270(45):27244-53. doi: 10.1074/jbc.270.45.27244.

Abstract

The major acceptors of sialic acid on the surface of metacyclic trypomastigotes, which are the infective forms of Trypanosoma cruzi found in the insect vector, are mucin-like glycoproteins linked to the parasite membrane via glycosylphosphatidylinositol anchors. Here we have compared the lipid and the carbohydrate structure of the glycosylphosphatidylinositol anchors and the O-linked oligosaccharides of the mucins isolated from metacyclic trypomastigotes and noninfective epimastigote forms obtained in culture. The single difference found was in the lipid structure. While the phosphatidylinositol moiety of the epimastigote mucins contains mainly 1-O-hexadecyl-2-O-hexadecanoylphosphatidylinositol, the phosphatidylinositol moiety of the metacyclic trypomastigote mucins contains mostly (approximately 70%) inositol phosphoceramides, consisting of a C18:0 sphinganine long chain base and mainly C24:0 and C16:0 fatty acids. The remaining 30% of the metacyclic phosphatidylinositol moieties are the same alkylacylphosphatidylinositol species found in epimastigotes. In contrast, the glycosylphosphatidylinositol glycan cores of both molecules are very similar, mainly Man alpha 1-2Man alpha 1-2Man alpha 1- 6Man alpha 1-4GlcN. The glycans are substituted at the GlcN residue and at the third alpha Man distal to the GlcN residue by ethanolamine phosphate or 2-aminoethylphosphonate groups. The structures of the desialylated O-linked oligosaccharides of the metacyclic trypomastigote mucin-like molecules, released by beta-elimination with concomitant reduction, are identical to the structures reported for the epimastigote mucins (Previato, J. O., Jones, C., Gonçalves, L. P. B., Wait, R., Travassos, L. R., and Mendoça-Previato, L. (1994) Biochem. J. 301, 151-159). In addition, a significant amount of nonsubstituted N-acetylglucosaminitol was released from the mucins of both forms of the parasite. Taken together, these results indicate that when epimastigotes transform into infective metacyclic trypomastigotes, the phosphatidylinositol moiety of the glycosylphosphatidylinositol anchor of the major acceptor of sialic acid is modified, while the glycosylphosphatidylinositol anchor and O-linked sugar chains remain essentially unchanged.

摘要

在昆虫媒介中发现的克氏锥虫的感染性形式即循环后期锥鞭毛体表面,唾液酸的主要受体是通过糖基磷脂酰肌醇锚定连接到寄生虫膜上的粘蛋白样糖蛋白。在此,我们比较了从循环后期锥鞭毛体和培养获得的非感染性上鞭毛体形式中分离出的糖基磷脂酰肌醇锚定的脂质和碳水化合物结构以及粘蛋白的O-连接寡糖。发现的唯一差异在于脂质结构。上鞭毛体粘蛋白的磷脂酰肌醇部分主要包含1-O-十六烷基-2-O-十六烷酰基磷脂酰肌醇,而循环后期锥鞭毛体粘蛋白的磷脂酰肌醇部分大多(约70%)是肌醇磷酸神经酰胺,由C18:0鞘氨醇长链碱基和主要是C24:0和C16:0脂肪酸组成。循环后期磷脂酰肌醇部分的其余30%与在上鞭毛体中发现的相同烷基酰基磷脂酰肌醇种类相同。相反,两种分子的糖基磷脂酰肌醇聚糖核心非常相似,主要是Manα1-2Manα1-2Manα1-6Manα1-4GlcN。聚糖在GlcN残基以及GlcN残基远端的第三个α-Man处被磷酸乙醇胺或2-氨基乙基膦酸酯基团取代。通过β-消除并伴随还原释放的循环后期锥鞭毛体粘蛋白样分子的去唾液酸化O-连接寡糖的结构与上鞭毛体粘蛋白报道的结构相同(普雷维亚托,J. O.,琼斯,C.,贡萨尔维斯,L. P. B.,韦特,R.,特拉瓦索斯,L. R.,和门多萨-普雷维亚托,L.(1994年)《生物化学杂志》301,151 - 159)。此外,从寄生虫两种形式的粘蛋白中都释放出大量未取代的N-乙酰葡糖胺醇。综上所述,这些结果表明,当上鞭毛体转变为感染性循环后期锥鞭毛体时,唾液酸主要受体的糖基磷脂酰肌醇锚定的磷脂酰肌醇部分发生了修饰,而糖基磷脂酰肌醇锚定和O-连接糖链基本保持不变。

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