Gregory Phillips Rose Hills
How the Ribosome Reads the Nascent Chain: The Role of Exit Tunnel Components in Elongation Arrest
As nascent proteins are synthesized, specific polypeptide sequences can interact with the ribosome exit tunnel to arrest translation, effectively stalling the ribosome. Importantly, stalling is sometimes dependent on small molecules raising the possibility that drugs may be designed to inhibit the synthesis of specific proteins implicated in disease. My research aims to explore the question of how both the amino acid sequence of a nascent polypeptide and the presence of a small molecule interact with the ribosome to arrest elongation. Specifically, the Arginine Attenuator Peptide elicits elongation arrest in the presence of arginine. I will mutate the yeast ribosome proteins L4, L17, and L10 by deleting the L17 and L4 loops of the constriction site (the narrowest part of the exit tunnel) and the portion of L10 in the peptidyl transferase center (the catalytic site of protein synthesis) and subsequently monitor stalling to further characterize the mechanism of elongation arrest.