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

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(RF)，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。我们从分子拟态和蛋白质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 eRF3)晶体结构和功能区注释3)EF-G和RRF在…上的功能相互作用3)23S rRNA的普遍保守的A2602对于肽释放活性的关键作用。4)酵母eRF3的部分Pron结构域掩盖了eRF3中的eRF3结合部位。1.5)核糖体蛋白L11结构域对与RF1和RF2的协同作用，6)酵母eRF3的N端结构域对eRF3的功能和稳定性的作用。3.7)RRF分解终止后的核糖体复合体，而不依赖于EF-G的核糖体转位酶活性。8)发现一种不依赖于Hsp104.9的新的[PSI^]蛋白变异体。4)构象记忆在传递到Sup35变异体的过程中保持在由弱到强或从强到弱的转换中。10)酿酒酵母Sup35的N端41-残基是[PSI^]Prion转导的物种屏障决定因素。11)基因组范围的筛选和因子的遗传选择包括HSP104和其他新的成分，负责维持酵母蛋白。较少

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