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

• 批准号: 8410079
• 负责人: NILGUN E TUMER
• 金额: $ 5.34万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8410079
• 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

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.

项目概要 这是罗格斯大学 Nilgun Tumer 博士合作的 FIRCA 申请 新泽西州新不伦瑞克大学和 Marek Tch¿rzewski 博士在玛丽亚居里 波兰斯克洛多夫斯卡大学。这项研究将在 Maria Curie Sklodowska 进行 波兰大学作为 NIH 拨款的延伸，编号为 R01-AI072425，2007 年 3 月 15 日至 2012 年 2 月 29 日。 此次合作利用了博士的独特资源和研究环境。 Tch¿rzewski 的实验室使用蓖麻毒素 A 链 (RTA) 作为分子工具来探测蓖麻毒素 A 链的功能 真核核糖体茎并鉴定茎结构的功能部分。尽管其 在蛋白质合成、真核生物茎的分子结构中具有根本重要性 由于缺乏适当的分子工具，其功能细节尚不清楚。博士。 Tch¿rzewski 开发了酵母菌株以及分离体内组装的方法 首次发现真核生物核糖体柄。从酵母中分离出整个天然茎 彻底改变了茎的制备方法并促进了对茎的功能的研究 真核生物核糖体柄。 Tumer 博士开发了模型系统来研究 蓖麻毒素 A 链 (RTA) 并发现 RTA 与核糖体柄结合以抑制蛋白质 合成。 Tumer 博士与 Tch¿rzewski 博士合作，展示了 RTA和分离的天然酵母核糖体茎，并获得初步数据证明 RTA可以作为一种非常具体的分子工具来探测结构和功能 真核生物茎。我们建议确定对结合 RTA 至关重要的茎成分，研究 RTA 与不同物种的茎复合物的相互作用，包括细菌、古细菌、 酵母和人类并鉴定茎结构的功能部分。此次合作将 将母基金中正在进行的 RTA 结构功能分析与生化联系起来， 在波兰 Tch¿rzewski 博士的实验室中对茎进行结构和遗传分析，并将提供 关于核糖体茎在蛋白质合成中的作用的新见解。