Specific Interactions of the Ribosome With the Nascent Peptide

核糖体可以特异性地识别某些新生肽。这种相互作用可以代表蛋白质合成的一般特征，可以影响翻译并在基因表达的调节中发挥作用。然而，这种相互作用的关键的核糖体和新生肽的性质的元素仍然在很大程度上是未知的。本研究的目的是了解细菌核糖体与短新生肽之间的功能相互作用导致核糖体在mRNA上停滞的分子机制。能够检测核糖体停滞的基因报告系统将用于鉴定阻止核糖体沿mRNA沿着的多种肽。将选择引起核糖体停滞的新生肽序列，并确定与核糖体功能相互作用的关键肽特征。遗传和生物化学分析将用于表征停滞复合物中的新生肽和参与与新生肽和停滞反应的特异性相互作用的核糖体元件。将评估其他细胞因子在核糖体停滞中的参与。将通过检查细菌基因组中停滞肽序列的出现来研究新生肽依赖性核糖体停滞的生理意义。该研究的更广泛影响将包括更好地了解蛋白质合成的基本机制，诱导抗生素耐药性的分子机制，并可能最终导致开发更好的抗生素。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.