Glycobiology of Leishmania

利什曼原虫的糖生物学

• 批准号: 7183476
• 负责人: Salvatore J Turco
• 金额: $ 36.27万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7183476
• 关键词: Anabolism; Automobile Driving; Biochemical; Bioinformatics; Competence; Complex; Enzymatic Biochemistry; Enzymes; Family; Funding; Galactosyltransferases; Genes; Genetic; Glycobiology; Glycoconjugates; Glycosylphosphatidylinositols; Golgi Apparatus; Grant; Health; Individual; Investigation; Leishmania; Leishmaniasis; Length; Life Cycle Stages; Location; Modification; Molecular; Molecular Chaperones; Numbers; Parasites; Pathway interactions; Polysaccharides; Proteins; Reaction; Role; Sand Flies; Side; Structure; Surface; Uridine Diphosphate Sugars; Virulence; base; genetic regulatory protein; glycosylation; glycosyltransferase; lipophosphonoglycan; metacyclogenesis; mutant; prototype; reconstitution; sugar; sugar nucleotide; transmission process

DESCRIPTION (provided by the applicant): Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a major health problem worldwide. Leishmania have evolved a unique family of phosphoglycan (PG)- containing glycoconjugates, including the GPI-anchored prototype lipophosphoglycan (LPG). The abundance, location, and uniqueness of the Leishmania glycoconjugates have implicated these molecules in critical roles for the parasite's survival in their harsh digenetic life cycle. Unfortunately, the wide distribution of PG units and GPI domains across a considerable number of diverse glycoconjugates has hindered a comprehensive assessment of their individual functions and the enzymes responsible for their biosynthesis. In a separately funded grant, we have surmounted this dilemma by isolating relevant genes via functional complementation of glycosylation mutants and cross-species manipulations. These studies have progressed sufficiently to enable us to focus this grant on the enzymology of the encoded proteins involved in glycoconjugate biosynthesis and expression, which in turn, represent indispensable opportunities toward scrutinizing the molecular pathways of glycoconjugate assembly in Leishmania. By fully characterizing key proteins encoded by selected genes, we expect to meaningfully advance our understanding of how Leishmania assemble such an assortment of complex, interrelated glycoconjugates and how they are biochemically involved in the parasite's life cycle. The specific aims of this competing renewal application are: 1. to investigate the family of Golgi nucleotide-sugar transporters. 2. to characterize the multiple mannosylphosphoryltransferases (MPTs) involved in PG synthesis. 3. to determinate the relationship of a chaperone with galactosylation of PG repeat units. 4. to examine the proteins involved in controlling LPG length and side chain sugar modifications

描述（由申请人提供）：利什曼原虫属原生动物寄生虫是利什曼病的病原体，利什曼病是世界范围内的一个主要健康问题。利什曼原虫已经进化出一个独特的含磷酸聚糖 (PG) 的糖复合物家族，包括 GPI 锚定的原型脂磷酸聚糖 (LPG)。利什曼原虫糖缀合物的丰富性、位置和独特性表明这些分子对于寄生虫在其严酷的双遗传生命周期中的生存发挥着关键作用。不幸的是，PG 单元和 GPI 结构域在大量不同的糖复合物中广泛分布，阻碍了对其各自功能和负责其生物合成的酶的全面评估。在一项单独资助的资助中，我们通过糖基化突变体的功能互补和跨物种操作分离相关基因，克服了这一困境。这些研究已经取得了足够的进展，使我们能够将这笔资助集中在参与糖复合物生物合成和表达的编码蛋白的酶学上，这反过来又代表了审查利什曼原虫糖复合物组装分子途径不可或缺的机会。通过充分表征选定基因编码的关键蛋白质，我们期望有意义地增进我们对利什曼原虫如何组装如此多种复杂的、相互关联的糖复合物以及它们如何在生化方面参与寄生虫生命周期的理解。 此竞争性续订申请的具体目标是： 1. 研究高尔基体核苷酸-糖转运蛋白家族。 2. 表征参与 PG 合成的多种甘露糖基磷酸转移酶 (MPT)。 3.确定伴侣与PG重复单元半乳糖基化的关系。 4. 检查参与控制 LPG 长度和侧链糖修饰的蛋白质