X-RAY STRUCTURE OF AFRICAN TRYPANOSOME SURFACE ANTIGENS

非洲锥虫表面抗原的 X 射线结构

• 批准号: 3131309
• 负责人: DON C WILEY
• 金额: $ 9.49万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3131309
• 关键词: Trypanosoma; X ray crystallography; carbohydrate structure; crystallization; electron microscopy; gel electrophoresis; glycoprotein structure; glycoproteins; high performance liquid chromatography; immunoglobulin genes; monoclonal antibody; protein structure; protozoal antigen; surface antigens; trypanosomiasis

The three-dimensional structure of a series of "variable surface glycoprotein" (VSG) antigens from the membrane of the unicellular parasite, Trypanosoma brucei, are being determined by high resolution X- ray crystallography. The African trypanosome evades the host immune response by sequentially expressing antigenically distinct VSGs, which form a protective coat on its surface. Just as the host responds to one foreign antigenic challenge, the trypanosome expresses a new antigenically distinct VSG, escaping neutralization by the host. Our goal is to understand the structure of this remarkable series of surface glycoproteins and their role in antigenic variation. African trypanosomes, which are spread by the tsetse fly, cause various forms of animal and human trypanosomiasis (sleeping sickness). These studies aim to describe the structure of the VSG protein and carbohydrate, the location and nature of the antigenic determinants, and should provide a molecular model of the VSG, which can be used for the rational design of drugs and/or vaccines. Currently, the structures of the variable N-Terminal domain of MITat 1.2 and ILTat 1.25 VSGs are being determined to 2.9 and 2.5A resolution respectively from crystals of the purified glycoproteins. Future studies on complexes with monoclonal antibody Fab fragments and on electron microscopic image analysis of the VSG coat are proposed.

一系列“变曲面”的三维结构 糖蛋白”（VSG）抗原从膜的单细胞 寄生虫，布氏锥虫，正在通过高分辨率X- 射线晶体学非洲锥虫逃避宿主免疫 通过顺序表达抗原性不同的VSG应答， 在其表面形成保护层。就像宿主对一个 外来抗原的挑战，锥虫表达了一种新的 抗原性不同的VSG，逃避宿主的中和作用。我们的目标 是了解这一系列非凡的表面结构 糖蛋白及其在抗原变异中的作用。 非洲锥虫由采采蝇传播， 动物和人类锥虫病（昏睡病）。这些 研究旨在描述VSG蛋白的结构， 碳水化合物、抗原决定簇的位置和性质，以及 应该提供一个分子模型的VSG，可用于 药物和/或疫苗的合理设计。 目前，MITat 1.2的可变N-末端结构域的结构 和ILTat 1.25 VSG被确定为2.9和2.5A分辨率 分别来自纯化的糖蛋白的晶体。未来的研究 在与单克隆抗体Fab片段的复合物上， 提出了VSG涂层的显微图像分析方法。