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硕大利什曼原虫无鞭毛体脂磷壁酸聚糖的结构

The structure of Leishmania major amastigote lipophosphoglycan.

作者信息

Moody S F, Handman E, McConville M J, Bacic A

机构信息

Walter and Eliza Hall Institute of Medical Research, Immunoparasitology Unit, Royal Melbourne Hospital, Victoria, Australia.

出版信息

J Biol Chem. 1993 Sep 5;268(25):18457-66.

PMID:8360147
Abstract

Intracellular amastigotes of Leishmania major produce 6 x 10(4) copies/cell of a lipophosphoglycan (LPG) that is structurally distinct from the LPG produced by the extracellular promastigote form of L. major, Leishmania donovani, and Leishmania mexicana (reviewed by McConville, M. J. (1991) Cell Biol. Int. Rep. 15, 779-798). L. major amastigote LPG is composed of a lysoalkyl phosphatidylinositol lipid anchor that links via a diphosphorylated hexasaccharide core to a phosphoglycan (6-100 kDa). The structures of the anchor, the core, and the phosphoglycan were determined by monosaccharide and linkage analysis, fast atom bombardment-mass spectrometry, one-dimensional 1H NMR spectroscopy, and exoglycosidase microsequencing. The lipid anchor contains predominantly 1-O-alkylglycerols with 24:0 and 22:0 alkyl chains. The lipids are linked via a glycerol-myo-inositol-PO4 to a core glycan with the structure -PO4-6)Gal(alpha 1-)Gal(alpha 1-) Galf(beta 1-)[Glc(alpha 1-PO4-)]Man(alpha 1-)Man(alpha 1-)GlcN(alpha 1-). The chromatographic characteristics of the core glycan suggest that the saccharide components are linked similarly in amastigote and promastigote LPG. The phosphoglycan attached to the core consists of -PO4-6)Gal(beta 1-4)Man(alpha 1- repeats units which are either unsubstituted (70%) or substituted (30%) at the 3-position of the Gal residues with oligosaccharide side chains containing primarily Gal and some Glc. Thirteen different types of side chains were identified with the structures [Gal(beta 1-3)]x, where x = 1-11, or Glc(1-3)Glc(1-3), or Glc(1-3)Gal(beta 1-3), where glucose is probably in the beta-configuration. All monosaccharides in the phosphoglycan domain are in the pyranose configuration. The average number of repeat units per molecule is 36. The nonreducing terminus of the phosphoglycan chains probably terminates predominantly in the neutral disaccharide Gal(beta 1-4)Man(alpha 1-. Comparison of the structure of L. major amastigote LPG to L. major promastigote procyclic and metacyclic LPG forms (McConville, M. J., Turco, S. J., Furguson, M. A. J., and Sacks, D. L. (1992) Embo J. 11, 3593-3600) indicates that this molecule is developmentally modified throughout the different stages of the parasites' life cycle.

摘要

硕大利什曼原虫的细胞内无鞭毛体产生6×10⁴拷贝/细胞的脂磷壁酸(LPG),其结构与硕大利什曼原虫、杜氏利什曼原虫和墨西哥利什曼原虫细胞外前鞭毛体形式产生的LPG不同(McConville, M. J. (1991) Cell Biol. Int. Rep. 15, 779 - 798综述)。硕大利什曼原虫无鞭毛体LPG由一个溶烷基磷脂酰肌醇脂质锚组成,该锚通过一个双磷酸化的六糖核心连接到一个磷酸聚糖(6 - 100 kDa)。通过单糖和连接分析、快原子轰击质谱、一维¹H NMR光谱和外切糖苷酶微测序确定了锚、核心和磷酸聚糖的结构。脂质锚主要含有带有24:0和22:0烷基链的1 - O - 烷基甘油。脂质通过甘油 - 肌醇 - PO₄连接到一个核心聚糖,其结构为 - PO₄ - 6)Gal(α1 - )Gal(α1 - ) Galf(β1 - )[Glc(α1 - PO₄ - )]Man(α1 - )Man(α1 - )GlcN(α1 - )。核心聚糖的色谱特征表明,糖组分在无鞭毛体和前鞭毛体LPG中的连接方式相似。连接到核心的磷酸聚糖由 - PO₄ - 6)Gal(β1 - 4)Man(α¹ - 重复单元组成,这些单元在Gal残基的3位要么未被取代(70%),要么被主要含有Gal和一些Glc的寡糖侧链取代(30%)。鉴定出了13种不同类型的侧链,其结构为[Gal(β1 - 3)]x,其中x = 1 - 11,或Glc(1 - 3)Glc(1 - 3),或Glc(1 - 3)Gal(β1 - 3),其中葡萄糖可能处于β构型。磷酸聚糖结构域中的所有单糖均为吡喃糖构型。每个分子的重复单元平均数量为36。磷酸聚糖链的非还原末端可能主要以中性二糖Gal(β1 - 4)Man(α1 - 终止。将硕大利什曼原虫无鞭毛体LPG的结构与硕大利什曼原虫前鞭毛体的前循环型和后循环型LPG形式进行比较(McConville, M. J., Turco, S. J., Furguson, M. A. J., and Sacks, D. L. (1992) Embo J. 11, 3593 - 3600)表明,该分子在寄生虫生命周期的不同阶段发生了发育修饰。

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