X-RAY STRUCTURE OF AFRICAN TRYPANOSOME SURFACE ANTIGENS

一系列“可变曲面”的三维结构 单细胞膜上的“糖蛋白”(VSG)抗原 布鲁氏锥虫是一种寄生虫，正在用高分辨率X-射线衍射仪进行鉴定。 射线结晶学。非洲锥虫逃避宿主免疫 通过顺序表达抗原性不同的VSG进行反应，该VSG 在它的表面形成一层保护层。就像主机对一个 国外抗原挑战，锥虫表达一种新的 抗原性独特的VSG，逃避宿主的中和。我们的目标 是为了理解这一引人注目的表面系列的结构 糖蛋白及其在抗原变异中的作用。 由采采蝇传播的非洲锥虫引起各种 各种形式的动物和人类锥虫病(昏睡病)。这些 研究的目的是描述VSG蛋白的结构和 碳水化合物、抗原决定簇的位置和性质，以及 应提供VSG的分子模型，该模型可用于 合理设计药物和/或疫苗。 目前，MITAT 1.2的可变N-末端结构域的结构 和ILTat 1.25 VSG将被确定为2.9和2.5A分辨率 分别从纯化的糖蛋白的晶体中分离得到。未来研究 关于单抗Fab片段的络合物及其电子 对VSG涂层进行了显微图像分析。

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.