Structural and functional study of translational release factor 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释放因子的结构和功能

• 批准号: 13308040
• 负责人: NAKAMURA Yoshikazu
• 金额: $ 29.45万
• 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 (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13308040/
• 关键词: molecular mimicry; translation termination; polypeptide release factor; peptide anticodon; stop codons; ribosome recycling factor; yeast prion; translational control

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, 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 translational release factors from the viewpoint of molecular mimicry and prion transmission, and uncovered the following aspects.1)Omnipotent decoding potential resides in eRF1 of variant-code organisms and is modulated by the interactions of amino acid seq … More uences within the domain 1.2)Polypeptide release at sense and noncognate stop codons by localized charge-exchange alterations in translational release factors.3)EF-G participates in ribosome disassembly by interacting with ribosome recycling factor RRF at their tRNA-mimicry domains.4)Yeast [PSI^+] prions that are crosstransmissible and susceptible beyond a species barrier through a quasi-prion state.5)The critical role of the universally conserved A2602 of 23S rRNA in the release of the nascent peptide during translation termination.6)Crystal structure and functional analysis of the eukaryotic class II release factor eRF3 from S.Pombe.7)Part of the prion domain of yeast eRF3 masks the eRF3-binding site in eRF1.8)RRF disassembles the posttermination ribosomal complex independent of the ribosomal translocase activity of EF-G.9)Heterologous expression of A.aeolicus RRF in E.coli is dominant lethal by forming a complex that lacks functional coordination for ribosome disassembly.10)Conformational memory preserved in a weak-to-strong or strong-to-weak [PSI^+] conversion during transmission to Sup35 prion variants. Less

最近的分子和结构研究，包括本实验室的研究表明，被称为翻译因子的蛋白质模仿tRNA的形状。其中一种是多肽释放因子，它编码一种三肽，作为“反密码子”来破译信使核糖核酸中的终止密码子。这些发现使我们能够提出蛋白质和RNA之间的大分子模拟的新概念。此外，发芽酵母的[psi^+]元件代表翻译释放因子eRF3的Prion构象，该转录释放因子在细胞质中繁殖和传递。在许多水平上，酵母蛋白与哺乳动物的蛋白类似，人们很有兴趣了解蛋白是如何在同基因菌株中产生变异的。我们从分子拟态和Prion传递的角度研究了翻译释放因子，发现了以下几个方面：1)全能的解码潜力存在于变异编码生物的eRF1中，并受氨基酸序列…的相互作用调节结构域内的更多功能1.2)通过翻译释放因子的局部电荷交换改变，在正义和非同源终止密码子上释放多肽。3)EF-G通过与核糖体回收因子rrf在其tRNA模拟结构域相互作用而参与核糖体的分解。4)酵母[psi^+]通过准蛋白状态跨物种传递和易感的Prion。5)23S rRNA的普遍保守的A2602在翻译终止过程中新生肽的释放中的关键作用。6)真核细胞II类释放因子eRF3的晶体结构和功能分析8)RRF分解终止后的核糖体复合体，而不依赖于EF-G.9)的核糖体转位酶活性。9)在大肠杆菌中异源表达的Aaeolicus RRF是显性致死的，因为它形成的复合体缺乏核糖体分解的功能配位。10)构象记忆在传递到Sup35蛋白变异体的过程中以从弱到强或从强到弱的[PSI^+]转换的方式保存。较少

项目成果

酵母プリオンの分子生物学

酵母朊病毒的分子生物学

• 发表时间: 2002
• 作者: M.Endo;M.Yamaguchi et al.;中村義一
• 通讯作者: 中村義一

Transient idling of posttermination ribosomes ready to reinitiate protein synthesis

• DOI: 10.1016/j.biochi.2004.08.006
• 发表时间: 2004-12-01
• 期刊: BIOCHIMIE
• 影响因子: 3.9
• 作者: Karamyshev, AL;Karamysheva, ZN;Nakamura, Y
• 通讯作者: Nakamura, Y

翻訳終結機構

翻译终止机制

• 发表时间: 2004
• 期刊: 「躍進するRNA研究」(中村義一, 塩見春彦編)、実験医学 22
• 作者: 伊藤耕一

Polypeptide release at sense and noncognate stop codons by localized charge-exchange alterations in translational release factors.

通过翻译释放因子中的局部电荷交换改变，在有义和非同源终止密码子处释放多肽。

• 发表时间: 2002
• 期刊: Proc. Natl. Acad. Sci. 99
• 作者: Uno;M.;Ito;K.;Nakamura;Y.
• 通讯作者: Y.

Structure of ribosomal protein L1 from Methanococcus thermolithotrophicus. Functionally important structural invariants on L1 surface.

嗜热甲烷球菌核糖体蛋白 L1 的结构。

• 发表时间: 2002
• 期刊: Acta Cryst. D58
• 作者: Nevskaya;N.;Tishchenko;S.;Paveliev;M.;Smolinskaya;Y.;Fedorov;R.;Piendl;W.;Nakamura;Y.;Toyoda;T.;Garber;M.;Nikonov;s
• 通讯作者: s