Interaction of ricin A chain with the ribosomal stalk

蓖麻毒素 A 链与核糖体柄的相互作用

基本信息

批准号：
8209110
负责人：
NILGUN E TUMER
金额：
$ 5.62万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8209110
关键词：
Apoptosis Archaea Architecture Bacteria Binding Biochemical Biological Models Cell Death Cells Collaborations Complex Data Defect Depurination Development Docking Environment Glycine decarboxylase Grant Human Induction of Apoptosis Link MAPK14 gene MAPK8 gene Mammalian Cell Messenger RNA Methods Modeling Molecular Molecular Probes Mutagenesis Myelin P2 Protein Nature New Brunswick New Jersey Parents Poland Preparation Procedures Protein Biosynthesis Proteins RNA Splicing Research Resistance Resources Ribosomal Proteins Ribosomal RNA Ribosomes Ricin Ricin A Chain Role Saccharomyces Shiga-Like Toxins Signal Pathway Signal Transduction Site Small Interfering RNA Spain Specificity Structure System Time United States National Institutes of Health Universities Yeasts base cytotoxicity genetic analysis in vivo insight mutant novel parent grant pokeweed antiviral protein prevent tool

项目摘要

PROJECT SUMMARY This is a FIRCA application for the collaboration between Dr. Nilgun Tumer at Rutgers University, New Brunswick, New Jersey and Dr. Marek Tch¿rzewski at the Maria Curie Sklodowska University in Poland. This research will be done at the Maria Curie Sklodowska University in Poland as an extension of NIH Grant No. R01-AI072425, 3-15-2007 to 2-29-2012. This collaboration makes use of the unique resources and research environment in Dr. Tch¿rzewski's lab to use ricin A chain (RTA) as a molecular tool to probe the function of the eukaryotic ribosomal stalk and to identify the functional part of the stalk structure. In spite of its fundamental importance in protein synthesis, the molecular architecture of the eukaryotic stalk and details of its function are not known due to the lack of appropriate molecular tools. Dr. Tch¿rzewski has developed the yeast strains and the methods to isolate the in vivo assembled eukaryotic ribosomal stalk for the first time. Isolation of the whole native stalk from yeast has revolutionized the method of stalk preparation and facilitated research on the function of the eukaryotic ribosomal stalk. Dr. Tumer has developed the model systems to study the activity of ricin A chain (RTA) and discovered that RTA binds to the ribosomal stalk to inhibit protein synthesis. In collaboration with Dr. Tch¿rzewski, Dr. Tumer showed direct interaction between RTA and the isolated native yeast ribosomal stalk, and obtained preliminary data demonstrating that RTA can be used as a very specific molecular tool to probe the structure and the function of the eukaryotic stalk. We propose to identify the stalk components critical for binding RTA, study the interaction of RTA with stalk complexes from different species, including bacteria, archaea, yeast and human and to identify the functional part of the stalk structure. This collaboration will connect the ongoing structure function analysis of RTA in the parent grant with biochemical, structural and genetic analysis of the stalk in Dr. Tch¿rzewski's lab in Poland and will provide new insights into the role of the ribosomal stalk in protein synthesis.

项目摘要这是Rutgers Nilgun Tumer博士之间合作的FIRCA申请大学，新不伦瑞克省，新泽西州和Maria Curie的MarekTch¿sewski博士波兰的Sklodowska大学。这项研究将在Maria Curie Sklodowska完成波兰大学作为NIH赠款编号R01-AI072425，3-15-2007至2-29-2012的扩展。这种合作利用了博士的独特资源和研究环境。 tch�Rzewski的实验室使用ricin a链（RTA）作为分子工具来探测功能真核核糖体茎并识别茎结构的功能部分。尽管有蛋白质合成中的基本重要性，真核茎的分子结构由于缺乏适当的分子工具，其功能的细节尚不清楚。博士 tch�Rzewski开发了酵母菌菌株和分离体内组装的方法真核核糖体茎首次。隔离整个本地茎与酵母的隔离彻底改变了缠扰准备的方法，并准备了关于真核核糖体茎。 Tumer博士开发了模型系统来研究 ricin A链（RTA），发现RTA与核糖体茎结合以抑制蛋白合成。在与TCH�Rzewski博士合作的情况下，Tumer博士在 RTA和孤立的天然酵母核糖体茎，并获得了初步数据该RTA可以用作探测结构和功能的非常特定的分子工具真核茎。我们建议确定对结合RTA至关重要的茎成分，研究 RTA与来自不同物种的茎复合物的相互作用，包括细菌，古细菌，酵母和人类，并确定茎结构的功能部分。这项合作将将父级授予中RTA的持续结构函数分析与生化， TCHSKI博士在波兰实验室的茎的结构和遗传分析，并将提供对核糖体茎在蛋白质合成中的作用的新见解。