BIOSYNTHESIS--TRYPANOSOME VARIANT SURFACE GLYCOPROTEIN

生物合成--锥虫变体表面糖蛋白

• 批准号: 3131327
• 负责人: PAUL T ENGLUND
• 金额: $ 16.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-05-01 至 1987-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3131327
• 关键词: O glycosidase; Trypanosoma; antibody; carbohydrate biosynthesis; chromatography; ethanolamines; high performance liquid chromatography; membrane lipids; nuclear magnetic resonance spectroscopy; oligosaccharides; phosphates; surface antigens

African trypanosomes are parasitic protozoa which are responsible for human and animal diseases. These parasites live in the host's bloodstream, and they escape the immune system by undergoing antigenic variation. Antigenic variation is mediated by a glycoprotein known as the Variant Surface Glycoprotein (VSG). This protein forms a dense surface coat which covers the entire cell. During antigenic variation the parasite synthesizes a new VSG, with a different amino acid sequence, and therefore exchanges its old coat for a new one. Each parasite has genetic potential to synthesize more than 100 different VSGs. The objective of this proposal is to study the biosynthesis, structure, and turnover of VSG. Emphasis will be directed towards the structure and synthesis of the moiety at the VSG C-terminus which contains carbohydrate, phosphate, ethanolamine, and probably lipid. This putative lipid presumably serves to anchor the VSG to the cell's plasma membrane. Specific aims include: 1) A study of the temporal sequence of processing events at the VSG C-terminus. Processing includes removal of a peptide sequence and attachment of sugars, phosphate, ethanolamine, and lipid. 2) A structural determination of the moiety at the C-terminus. 3) A search for an enzyme that cleaves the lipid from the VSG and therefore releases these molecules from the cell. This enzyme may be involved in the exchange of surface coats during antigenic variation, and it may be highly regulated so as not to release the surface coat at inappropriate times. These studies may lead to the discovery of biochemical structures and pathways which are unique to trypanosomes. This knowledge may lead to new modes of chemotherapy against these parasites.

非洲锥虫是寄生的原生动物，是人类的 和动物疾病。 这些寄生虫生活在宿主的血液中， 它们通过经历抗原性变异来逃脱免疫系统。 抗原 变异是由称为变异表面的糖蛋白介导的 糖蛋白（VSG）。 该蛋白质形成密集的表面涂层 整个单元格。 在抗原变异期间，寄生虫合成了一个新的 VSG，具有不同的氨基酸序列，因此交换了其旧 新的外套。 每个寄生虫具有合成更多的遗传潜力 大于100个不同的VSG。 该建议的目的是研究生物合成，结构和 VSG的营业额。 重点将针对结构和 在含有碳水化合物的VSG C末端的部分合成部分， 磷酸盐，乙醇胺，可能是脂质。 这种推定的脂质 大概是将VSG固定在细胞的质膜上。 具体目的包括：1）对处理时间顺序的研究 VSG C末端的事件。 加工包括去除肽 糖，磷酸盐，乙醇胺和脂质的序列和附着。 2） 在C末端的部分的结构确定。 3）搜索 对于从VSG裂解脂质并因此释放的酶 这些分子来自细胞。 该酶可能参与交换 抗原变异期间的表面涂层，并且可能受到高度调节 以免在不适当的时间释放表面涂层。 这些研究可能导致发现生化结构和 锥虫独有的途径。 这些知识可能导致新的知识 对这些寄生虫的化学疗法模式。