Structure and Function of E. histolytica Adherence Lectin

溶组织内阿米巴粘附凝集素的结构和功能

基本信息

批准号：
7567580
负责人：
William A Petri
金额：
$ 36.87万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7567580
关键词：
1-Phosphatidylinositol 3-Kinase Active Sites Adherence Amebiasis Amebic colitis Antibodies Antigenic Variation Apoptotic Behavior Binding Biochemical Biochemistry Biology Cell Surface Receptors Cells Chimera organism Code Complex Controlled Environment Cytoplasmic Tail Dominant-Negative Mutation Endocytosis Entamoeba histolytica Enteral Environment Epithelial Cells Escherichia coli Extracellular Domain Family Gal-GalNAc Galactose Gene Family Genome Genomics Human IL2RA gene Immune Sera In Vitro Infection Ingestion Interleukin 2 Receptor Intestines Invaded Knowledge Lectin Life Liver Abscess Measurement Measures Messenger RNA Modeling Mucins Mus Mutation Organism Parasite Control Parasites Peptides Phagosomes Phosphotransferases Prevention Process Property Protein Kinase Proteins Proteome Proteomics Reaction Regulation Research Personnel Role Signal Transduction Specificity Structure System Testing World Health Organization Yeasts base cDNA Library innovation insight killings knock-down laser capture microdissection member novel novel strategies positional cloning programs receptor yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Amebic colitis and liver abscess are due to infection with the enteric protozoan parasite Entamoeba histolytica. The World Health Organization estimates that approximately 50 million people worldwide suffer from invasive amebic infection each year. The adherence of E. histolytica trophozoites to intestinal mucins and epithelial cells by a galactose-binding (Gal/GalNAc) lectin is necessary for the parasite to kill host cells and invade. We have discovered that the intermediate subunit of this lectin is part of an E. histolytica gene family of more than 80 transmembrane kinases (TMK). The TMK kinase domains are novel and the number of TMKs is unprecedented in a unicellular organism. We hypothesize that the TMKs are a major receptor system for sensing the environment and controlling the invasive behavior of the parasite. We propose to test if the TMKs undergo antigenic variation, determine if TMK 96 is a dual specificity (tyr and ser/thr) kinase and identify its downstream effectors and regulators, and study the biologic activities regulated by TMK 96. We will focus on the role of TMK 96 in the adherence, killing and endocytosis of apoptotic corpses as it has been identified as part the phagosome proteome. Successful completion of these studies will provide fundamental knowledge of these novel receptor kinases and insight into the means by which the parasite controls its invasion into the human intestine.

描述（由申请人提供）：amebic结肠炎和肝脓肿是由于肠道原生动物寄生虫的感染而引起的。世界卫生组织估计，全世界约有5000万人每年都患有侵入性阿米比奇感染。寄生虫杀死宿主细胞并入侵是必要的，需要通过半乳糖结合（GAL/GALNAC）凝集素（GAL/GALNAC）凝集素粘附于肠道粘蛋白和上皮细胞对肠道粘蛋白和上皮细胞的遵守。我们发现该凝集素的中间亚基是80多个跨膜激酶（TMK）的溶组织溶液基因家族的一部分。 TMK激酶结构域是新颖的，在单细胞生物中，TMK的数量是前所未有的。我们假设TMK是感测环境并控制寄生虫的侵入性行为的主要受体系统。 We propose to test if the TMKs undergo antigenic variation, determine if TMK 96 is a dual specificity (tyr and ser/thr) kinase and identify its downstream effectors and regulators, and study the biologic activities regulated by TMK 96. We will focus on the role of TMK 96 in the adherence, killing and endocytosis of apoptotic corpses as it has been identified as part the phagosome蛋白质组。这些研究的成功完成将为这些新型受体激酶提供基本知识，并深入了解寄生虫控制其入侵人类肠道的手段。