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Functional Analysis of the T. gondii AMA1 Cytosolic Tail

刚地弓形虫 AMA1 胞质尾的功能分析

基本信息

批准号：
8630571
负责人：
GARY E WARD
金额：
$ 38.13万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-11-15 至 2018-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8630571
关键词：
Acquired Immunodeficiency Syndrome Acute Address Affect Aldehyde-Lyases American Animal Model Antigens Apical Attention Binding Binding Proteins Biological Assay Biological Process C-terminal Cause of Death Cell membrane Cell surface Cells Cleaved cell Cryptosporidiosis Cytosol Disease Event Experimental Models Extracellular Domain Goals Human Hybrids Immunocompromised Host Individual Infection Integral Membrane Protein Invaded Life Life Cycle Stages Ligands Link Malaria Malaria Vaccines Mediating Mutation Names Organelles Parasites Pathogenesis Phosphorylation Play Population Pregnancy Protein Binding Proteins Research Role Signal Pathway Signal Transduction Staging Surface Tail Testing Toxoplasma gondii Toxoplasmosis Transmembrane Domain Work Yeasts apical membrane cost design drug development foodborne illness genetic analysis in vivo knowledge of results novel novel strategies pathogen prevent protein function public health relevance receptor research study vaccine candidate vaccine development

项目摘要

Toxoplasma gondii is a widespread protozoan parasite that causes debilitating and sometimes life- threatening disease during pregnancy and in immunocompromised individuals, including those with AIDS. Toxoplasmosis is the second most common cause of death by foodborne illness in the USA and costs the economy billions of dollars annually. T. gondii is also a valuable experimental model for related apicomplexan parasites, including those that cause malaria and cryptosporidiosis. Host cell invasion is essential to the parasite's life cycle, and apical membrane antigen1 (AMA1) is a highly conserved transmembrane protein on the parasite surface that plays an important role in invasion. Much is known about how the extracellular domain of AMA1 interacts with its ligand on the host cell surface (RON2) during invasion, but surprisingly little is known about the function of its short, C-terminal tail, which is located in the parasite cytosol. The central hypothesis of this project is that the cytosolic tail of T. gondii AMA1 (TgAMA1) functions in invasion-related signaling pathways, through interaction with other parasite proteins. The Aims of the project are to: (a) Determine the phenotypic consequences of specific mutations in the TgAMA1 cytosolic tail, establishing at what step(s) in invasion the cytosolic tail functions and the specific residues involved; (b) Identify and determine the biological function of proteins that interact with the TgAMA1 cytosolic tail, establishing whether tail mutations that disrupt invasion also affect the binding of specific proteins; and (c) Determine whether the binding of TgAMA1 to TgRON2 triggers intracellular signaling mediated by the TgAMA1 cytosolic tail, resulting in invasion-related changes to the parasite phosphoproteome. These studies address a significant gap in our understanding of the role that AMA1 plays in the invasion of host cells by apicomplexan parasites. A more complete understanding of AMA1 function will generate new approaches to preventing or controlling the devastating diseases caused by this important group of human pathogens.

刚地弓形虫是一种广泛存在的原生动物寄生虫，它会导致身体虚弱，有时甚至导致死亡