UBC Math Bio Seminar: Shiqi Yu

The ribosome exit tunnel is a sub-compartment of the ribosome that contains the nascent polypeptide chain and as such, is involved in the regulation of translation other essential functions such as protein folding. Analyzing and comparing the geometry of the tunnel from high resolution structures reveal key differences between eukaryotes and prokaryotes: eukaryotic tunnels are overall shorter and narrower, with the presence of a second constriction site that is absent in prokaryotes. To understand the potential implications of these differences on the translation of short proteins (sORFs), we used molecular simulations to study the escape process of various coarse-grained protein models, in a confined domain that captures key geometric features of the tunnel. Our simulations reveal that the escape process is critically impacted, with a probability of escape and conditional escape time that vary across sequence lengths, and between domains of life. Upon analyzing the nascent chain trajectories and energy profiles, we precisely explain why the escape process varies for proteins of different lengths under the effect of the constriction sites in the ribosomal tunnel. Further sequence analysis of from Ribosome Profiling Data show that the number of the proteins around 12 amino acids is the lowest in both human and Ecoli, suggesting a greater selection pressure for sORFs at specific lengths during biological evolution.