Molecular Interplay at the Ribosome Exit Site

Accumulating data have showed that the ribosome exit site is a crowded environment where many factors rendezvous, including chaperones, modification enzymes, and protein targeting and translocation machineries. Even post-translational targeting factors, such as Bag6 and SecA, contact the ribosome. Many of these factors interact with the ribosome via the same protein, L23, and recognize hydrophobic segments on nascent proteins. How nascent proteins engage distinct factors and commit to the correct biogenesis pathways is an emerging key question at the heart of accurate protein biogenesis.

Building on our expertise in understanding molecular events on the ribosome, we are beginning to explore the inner workings of other protein biogenesis machineries, and decipher how the SRP compete or cooperate with them to ensure the proper biogenesis of nascent proteins. Ultimately, we aim to develop a comprehensive and quantitative model that can accurately explain, or even predict, what happens to a nascent protein as it emerges from the ribosome, and how genetic and environmental factors impact these decision-making processes. Understanding at this level is crucial for establishing causal links to disease, and identifying new approaches of intervention.

Selected Publications:

  • Ariosa A.R., Lee J.H., Wang S., Saraogi I., and Shan S.O.(2015) Proc. Natl. Acad. Sci. "Regulation by a chaperone improves substrate selectivity during cotranslational protein targeting." PMID: 26056263.