THE MEMBRANE FORM OF VARIANT SURFACE GLYCOPROTEINS OF TRYPANOSOMA-BRUCEI
THE MEMBRANE FORM OF VARIANT SURFACE GLYCOPROTEINS OF TRYPANOSOMA-BRUCEI
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DOI：
10.1038/302349a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
TURNER, MJ
中科院分区：
文献类型：
--
作者：
DEALMEIDA, MLC;TURNER, MJ
非洲锥虫是一种寄生原生动物，其表面被一层相同糖蛋白分子的基质所包裹。这些变异表面糖蛋白 (VSG) 的组成发生变化，使得寄生虫能够逃脱宿主的免疫系统，从而导致有效的免疫预防变得不可能2-5。然而，在表面涂层之下，所有变异抗原类型都含有共同的膜成分6，其中一些可以通过替代途径激活补体7，导致未包被的锥虫裂解。因此，刺激体内VSG释放应该是一种潜在的化疗形式，因此我们研究了VSG附着在质膜上的模式。锥虫破裂后从细胞表面释放后纯化的材料已对来自多个物种的 VSG 进行了生化表征8-11。我们在此证明，布氏锥虫的 VSG 当与膜结合时，其存在形式在生物化学和免疫化学上都不同于以常规方式纯化的 VSG。细胞破裂后，膜形式 VSG (mfVSG) 被酶促转化为通常分离的水溶性释放形式 (sVSG)。在不发生这种修饰的条件下，纯化的 VSG 具有两亲特性，并且根据电荷转移电泳的标准表现为完整的膜蛋白。两种形式之间的差异在于 C 末端结构域，两种形式均被磷酸化。 sVSG 中的该结构域包含一种称为交叉反应决定簇 (CRD) 的免疫原性寡糖，连接到 C 端氨基酸12。抗CRD抗体对该决定簇的识别在膜形式中受到损害。
African trypanosomes are parasitic protozoa which are enveloped by a surface coat consisting of a matrix of identical glycoprotein molecules1. Variations in the composition of these variant surface glycoproteins (VSGs) allow the parasite to escape the host's immune system and render effective immunoprophylaxis improbable2–5. However, underlying the surface coat, all variant antigen types contain common membrane components6, some of which can activate complement by the alternative pathway7, leading to lysis of uncoated trypanosomes. Hence, stimulation of VSG releasein vivoshould be a potential form of chemotherapy, and we have therefore investigated the mode of attachment of VSG to the plasma membrane. Biochemical characterization of VSGs from several species has been performed on material purified after release from the cell surface following rupture of the trypanosome8–11. We demonstrate here that VSGs ofTrypanosoma bruceiwhen bound to the membrane exist in a form which differs both biochemically and immunochemically from VSGs purified in the conventional manner. After rupture of the cell, membrane-form VSG (mfVSG) is enzymatically transformed into the commonly isolated water-soluble released form (sVSG). In conditions in which this modification does not take place, purified VSGs have amphiphilic properties and behave as integral membrane proteins by the criterion of charge-shift electrophoresis. The difference between the two forms lies in the C-terminal domain, which is phosphorylated in both forms. This domain in sVSGs contains an immunogenic oligosaccharide known as the cross-reacting determinant (CRD), attached to the C-terminal amino acid12. Recognition of this determinant by anti-CRD antibodies is impaired in the membrane form.