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克氏锥虫的糖基磷脂酰肌醇:结构、生物合成及免疫生物学

Glycoinositolphospholipid from Trypanosoma cruzi: structure, biosynthesis and immunobiology.

作者信息

Previato Jose O, Wait Robin, Jones Christopher, DosReis George A, Todeschini Adriane R, Heise Norton, Previato Lucia Mendonça

机构信息

Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Bloco G, Universidade Federal do Rio de Janeiro, 21 944 970-Ilha do Fundão, Cidade Universitária, Rio de Janeiro, RJ, Brazil.

出版信息

Adv Parasitol. 2004;56:1-41. doi: 10.1016/s0065-308x(03)56001-8.

Abstract

The pathogenic protozoan parasite Trypanosoma cruzi expresses on its surface an unusual family of glycoinositolphospholipids (GIPLs) closely related to glycosylphosphatidylinositol (GPI) anchors. Different parasite isolates express distinct GIPLs which fall into two series, depending on the substitution of the third mannosyl residue in the conserved glycan sequence Man4-(AEP)-GlcN-InsPO4 by ethanolamine phosphate or beta-galactofuranose. Although the exact role of these molecules in the cell biology and pathogenicity of T. cruzi remains unknown, the lipid and glycan moieties impart distinct responses to host T and B lymphocytes and phagocytes, overall favouring an immune response permissive to the parasite. The biosynsthesis of GIPLs follows a pathway similar to that observed for GPI anchors. However, a more detailed understanding might enable the development of specific inhibitors of parasite-specific enzymes and lead to novel drugs to ameliorate Chagas disease.

摘要

致病性原生动物寄生虫克氏锥虫在其表面表达了一族不同寻常的糖基肌醇磷脂(GIPLs),它们与糖基磷脂酰肌醇(GPI)锚密切相关。不同的寄生虫分离株表达不同的GIPLs,这些GIPLs可分为两个系列,这取决于保守聚糖序列Man4-(AEP)-GlcN-InsPO4中第三个甘露糖基残基是被磷酸乙醇胺还是β-半乳呋喃糖取代。尽管这些分子在克氏锥虫的细胞生物学和致病性中的确切作用尚不清楚,但脂质和聚糖部分对宿主T淋巴细胞、B淋巴细胞和吞噬细胞产生不同的反应,总体上有利于对该寄生虫产生允许性免疫反应。GIPLs的生物合成遵循一条与GPI锚类似的途径。然而,更深入的了解可能有助于开发针对寄生虫特异性酶的特异性抑制剂,并催生用于改善恰加斯病的新型药物。

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