Specific Interactions of the Ribosome With the Nascent Peptide

核糖体可以识别特定的新生多肽。这种相互作用可以代表蛋白质合成的一般特征，可能会影响翻译，并在基因表达的调节中发挥作用。然而，核糖体的元素和对这种相互作用至关重要的新生多肽的性质在很大程度上仍不清楚。本研究的目的是了解细菌核糖体与新生短肽之间功能相互作用导致核糖体停滞于mRNA的分子机制。能够检测核糖体停滞的基因报告系统将被用来识别各种阻止核糖体沿着mRNA前进的多肽。将选择导致核糖体停滞的新生多肽序列，并确定与核糖体功能相互作用的关键多肽特征。遗传和生化分析将被用来表征失速复合体中的新生多肽，以及参与与新生多肽和失速反应特定相互作用的核糖体元件。其他细胞因素在核糖体停滞中的作用将被评估。将通过检测细菌基因组中出现的停滞肽序列来研究新生多肽依赖的核糖体停滞的生理学意义。这项研究的更广泛影响将包括更好地理解蛋白质合成的基本机制，诱导抗生素耐药性的分子机制，并可能最终导致更好的抗生素的开发。该项目将为博士后、研究生和本科生提供培训。

The ribosome can specifically recognize certain nascent peptides. Such interactions, which can represent a general feature of protein synthesis, may affect translation and play a role in regulation of gene expression. However, the elements of the ribosome and properties of the nascent peptide critical for such interactions remain largely unknown. The aim of this research is to understand the molecular mechanisms of the functional interactions between the bacterial ribosome and short nascent peptides that result in the ribosome stalling on mRNA. The gene reporter system capable of detecting ribosome stalling will be used to identify a variety of peptides that prevent ribosome progression along the mRNA. The nascent peptide sequences that cause ribosome stalling will be selected and peptide characteristics critical for functional interactions with the ribosome will be determined. Genetic and biochemical analyses will be used to characterize the nascent peptide in the stalled complex and the elements of the ribosome that are involved in specific interactions with the nascent peptide and the stalling response. Involvement of other cellular factors in the ribosome stalling will be assessed. The physiological significance of the nascent peptide-dependent ribosome stalling will be investigated by examining the occurrence of the stalling peptide sequences in bacterial genomes. The broader impact of the study will include a better understanding of the fundamental mechanisms of protein synthesis, molecular mechanisms of inducible antibiotic resistance and may eventually lead to development of better antibiotics. The project will provide training for post doctoral, graduate and undergraduate students.