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

• 批准号: 7210420
• 负责人: William A Petri
• 金额: $ 37.6万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 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/7210420
• 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; Invasive; Knowledge; Lectin; Life; Liver Abscess; Measurement; Measures; Messenger RNA; Modeling; Mucins; Mus; Mutation; Numbers; 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

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（申请人提供）：阿米巴结肠炎和肝脓肿是由于肠道原生动物寄生虫溶组织内阿米巴感染所致。世界卫生组织估计，全世界每年约有 5000 万人遭受侵袭性阿米巴感染。溶组织内阿米巴滋养体通过半乳糖结合 (Gal/GalNAc) 凝集素粘附在肠道粘蛋白和上皮细胞上，对于寄生虫杀死宿主细胞和入侵是必要的。我们发现该凝集素的中间亚基是溶组织内阿米巴基因家族的一部分，该家族拥有 80 多种跨膜激酶 (TMK)。 TMK 激酶结构域是新颖的，并且 TMK 的数量在单细胞生物中是前所未有的。我们假设 TMK 是感知环境和控制寄生虫入侵行为的主要受体系统。我们建议测试TMK是否发生抗原变异，确定TMK 96是否是双特异性（tyr和ser/thr）激酶并鉴定其下游效应子和调节子，并研究TMK 96调节的生物活性。 TMK 96 在凋亡尸体的粘附、杀伤和内吞作用中的作用，因为它已被鉴定为吞噬体蛋白质组的一部分。这些研究的成功完成将提供这些新型受体激酶的基础知识，并深入了解寄生虫控制其侵入人类肠道的方式。