Correlated Movement of tRNA and the Ribosome during Elongation

Abstract

The ribosome is a large RNA-protein complex, and it is the sole producer of protein in a cell. Accommodation is a key conformational change that allows movement of tRNA into the ribosome. To understand the accommodation process, it is central to quantify the energetic and structural content of the transition state ensemble. Previous studies have shown that the elbow-to-elbow distance between U8 of the P-site tRNA and U60 of aa-tRNA can capture the correct number of barrier-crossing events and movement along this coordinate is diffusive. Previous simulations have shown that the free-energy barrier during accommodation is predominantly due to the shape of the accommodation corridor. To explore the relationship between tRNA barrier-crossing events and fluctuations in the ribosome, we tested the degree to which these fluctuations are predictive of accommodation events. From this analysis, we have found that specific fluctuations in the corridor are strongly correlated with the process of aa-tRNA accommodation. We also found that the barrier-crossing events are accompanied by bending and contraction of the aa-tRNA. The coordinate analysis methods employed here can be applied to study correlated movements that are involved in other bimolecular processes, e.g. tRNA translocation. Furthermore, the identified coordinates can potentially be used in the experimental studies to indirectly monitor the process of aa-tRNA accommodation, and possible allow for precise control of the dynamics.