Finishing up a lingering project from your PhD almost a year into your postdoc is a great feeling, especially when it has actually been about 3 years in the making.

Though somewhat outside of the usual scope of activities in OPIG, I encourage you to take a look if the below summary grabs your interest. The full paper and supporting materials (including some movies which took entirely too long to make) can be found at https://pubs.acs.org/doi/abs/10.1021/jacs.9b12264.

Proteins are synthesized during the translation cycle, which is broken up into four phases: (i) initiation, (ii) elongation, (iii) termination, and (iv) ribosome recycling. In this paper, my co-authors and I used a combination of multi-scale molecular dynamics, bioinformatics, and gene ontology analysis to study the process of nascent protein ejection from the exit tunnel during the termination phase. The timescales of many of the steps of translation have been well characterized, but nascent protein ejection (defined here as the process of the nascent protein leaving the exit tunnel after its bond to the A-site tRNA is cleaved with the help of a release factor) had not been previously studied in detail.

We found that ejection times span at least three orders of magnitude in E. coli and that electrostatic interactions appear to be the main driving force of this large difference. Proteins we predicted to be slow ejecting based on their electrostatic characteristics also have more reads in ribosome profiling experiments at their stop codon. Finally, we determined using gene ontology analysis that predicted slow ejecting proteins are highly enriched in ribosomal proteins, suggesting that slow ejection may play a role in the co-translational assembly of ribosomes.

Citation

D. A. Nissley, Q. Vu, F. Trovato, N. Ahmed, Y. Jiang, M. S. Li and E. P. O’Brien. “Electrostatic interactions govern extreme nascent protein ejection times from ribosomes and can delay ribosome recycling.” J. Am. Chem. Soc., 2020, 142, 13, 6103-6110.