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Structural and functional study of translation apparatus from the viewpoint of molecular mimicry and prion transmission

从分子拟态和朊病毒传播的角度研究翻译装置的结构和功能

基本信息

批准号：
14035207
负责人：
NAKAMURA Yoshikazu
金额：
$ 83.78万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2006
项目状态：
已结题

项目摘要

Recent molecular and structural studies including those from this laboratory have revealed that proteins called translation factors mimic the shape of tRNA. One of them, a polypeptide release factor (RF), encodes a tripeptide that serves as an ‘anticodon' to decipher stop codons in mRNA. These findings let us to propose the novel concept of macromolecular mimicry between protein and RNA. Moreover, The [PSI^+] element of budding yeast represents the prion conformation of translation release factor eRF3 that is propagated and transmitted in the cytoplasm. On many levels, yeast prions are analogous to mammalian prions and much interest lies in understanding how prions are able to generate variation in isogenic strains. We have investigated RFs and ribosome-recycling-factor (RRF) from the viewpoint of molecular mimicry and prion transmission, and uncovered the following aspects.1) Crystal structure and functional domain annotation of S. Pombe eRF3.2) Functional interplay of EF-G and RRF at … More their tRNA-mimicry domains.3) The critical role of the universally conserved A2602 of 23S rRNA for the peptide-release activity.4) Part of the prion domain of yeast eRF3 masks the eRF3-binding site in eRF1.5) The role of ribosomal protein L11 domains for the cooperative interaction with RF1 and RF2, responsible for translation termination.6) The role of nonprion-state N-terminal domain of yeast eRF3 for functionality and stability of eRF3.7) RRF disassembles the posttermination ribosomal complex independent of the ribosomal translocase activity of EF-G.8) Discovery of a novel [PSI^+] prion variant that is independent of Hsp104.9) Conformational memory preserved in a weak-to-strong or strong-to-weak [PSI^+] conversion during transmission to Sup35 prion variants.10) The N-terminal 41-residue domain of S. cerevisiae Sup35 is a species-barrier determinant for [PSI^+] prion transmission.11) Genome-wide screening and genetic selection for factors, including Hsp104 and other novel components, responsible for the maintenance of yeast prions. Less

最近的分子和结构研究，包括本实验室的研究，揭示了被称为翻译因子的蛋白质模仿tRNA的形状。其中之一，多肽释放因子（RF），编码一个三肽，作为“反密码子”来破译mRNA中的终止密码子。这些发现使我们提出了蛋白质和RNA之间的大分子模拟的新概念。此外，芽殖酵母的[PSI^+]元件代表翻译释放因子eRF 3的朊病毒构象，其在细胞质中繁殖和传递。在许多层面上，酵母朊病毒类似于哺乳动物朊病毒，许多兴趣在于了解朊病毒如何能够在同基因菌株中产生变异。我们从分子模拟和朊病毒传递的角度研究了核糖体循环因子（RRF）和核糖体循环因子（RRF），发现了以下几个方面：1）S. Pombe eRF 3.2）EF-G和RRF的功能相互作用， ...更多信息它们的tRNA模拟结构域; 3）23 S rRNA的普遍保守的A2602对肽释放活性的关键作用; 4）酵母eRF 3的部分朊病毒结构域掩盖了eRF 1中的eRF 3结合位点; 5）核糖体蛋白L11结构域在与RF 1和RF 2的协同相互作用中的作用，6）酵母eRF 3的非朊病毒状态N-末端结构域对eRF 3的功能性和稳定性的作用。7）RRF不依赖于EF的核糖体移位酶活性而分解终止后核糖体复合物。G.8）发现了一种新的不依赖于Hsp 104的[PSI^+]朊病毒变异体。9）在向Sup 35朊病毒变异体传递过程中，[PSI^+]在弱到强或强到弱的转换中保留了构象记忆。酿酒酵母Sup 35是[PSI^+]朊病毒传播的物种屏障决定子。11）对包括Hsp 104和其他新组分在内的负责维持酵母朊病毒的因子进行全基因组筛选和遗传选择。少