Specific Interactions of the Ribosome With the Nascent Peptide

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

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.