RECOGNITION OF THE CS PROTEIN BY LIVER CELL RECEPTOR

该计划项目的主题是对 识别子孢子配体的机制，即第II区+ 环子孢子(CS)蛋白，硫酸乙酰肝素蛋白多糖(HSPG) 受体，位于肝细胞质膜上。我们的最终目标是 项目是为发展提供合理的基础 预防疟疾的化学预防和免疫预防药物 感染。本计划项目由三个项目和一个 行政以及S三大科技核心： 项目1-CS蛋白II-+区域的结构和功能。 它的主要目标是更准确地定义子孢子配体，即， CS蛋白的II+区基序及其结构相关性 其与HSPG受体的结合亲和力。 项目2-CS蛋白的肝脏受体的结构和功能。 本项目旨在鉴定与CS结合的HSPG的核心蛋白 以及封口链的结构和组成。 项目3-CS配体及其肝细胞的免疫学研究 受体。它的主要目标是定义免疫原可以诱导 阻断子孢子与其受体相互作用的抗体 在肝细胞上。 行政核心将提供行政支持和科学 协调所有项目。 科学/技术中心将提供啮齿动物疟疾的子孢子 [昆虫核心-b]、合成肽和MAP[多肽合成 设施-c]，以及为所有人提供的EM支持[EM设施-核心d] 三个项目。

The main theme of the Program Project is the characterization of the mechanism of recognition of a sporozoite ligand, the region II-plus of the circumsporozoite (CS) protein, by heparan sulfate proteoglycan (HSPG) receptors, on the plasma membrane of hepatocytes. The ultimate goal of our projects is to provide a rational basis for the development of chemoprophylactic and immunoprophylactic agents which can prevent malaria infection. This Program Project consists of three projects and an administrative as well s three Scientific/technical Cores: Project 1 - Structure and function of region II-plus of the CS protein. Its main objective is to define more precisely the sporozoite ligand, i.e., the region II-plus motif of the CS protein and to correlate its structural features with its binding affinity for the HSPG receptor. Project 2 - Structure and function of the liver receptor of CS protein. This project aims to characterize the core protein of the CS-binding HSPG and the structure and composition of the GAG chains. Project 3 - Immunological study of the CS ligand and its liver cell receptor. Its main objective is to define immunogens that can induce antibodies which block the interaction of sporozoites with their receptor on liver cells. The Administrative core will provide administrative support and scientific coordination ot all projects. The Scientific/Technical cores will provide sporozoites of rodent malaria [Insectary core - b], synthetic peptides and MAPs [Peptide synthesis facility - c], as well as E.M. support [E.M. facility - core d] for all three projects.