Document Type
Article
Publication Date
8-14-2024
Keywords
protein synthesis, ribosome translocation
Abstract
Abstract
Translocation in protein synthesis entails the efficient and accurate movement of the mRNA-[tRNA]2 substrate through the ribosome after peptide bond formation. An essential conformational change during this process is the swiveling of the small subunit head domain about two rRNA ‘hinge’ elements. Using iterative selection and molecular dynamics simulations, we derive alternate hinge elements capable of translocation in vitro and in vivo and describe their effects on the conformational trajectory of the EF-G-bound, translocating ribosome. In these alternate conformational pathways, we observe a diversity of swivel kinetics, hinge motions, three-dimensional head domain trajectories and tRNA dynamics. By finding alternate conformational pathways of translocation, we identify motions and intermediates that are essential or malleable in this process. These findings highlight the plasticity of protein synthesis and provide a more thorough understanding of the available sequence and conformational landscape of a central biological process.
Author summary
Translocation, the motion of the ribosome across its mRNA substrate, is an essential stage of protein synthesis. A key conformational change in this process is the rotation of the ribosome head domain about two rRNA hinges in the direction of translocation, repositioning the mRNA and tRNAs in their final states. Employing iterative selection, we obtain variant hinges capable of performing translocation in vitro and in vivo. Through molecular dynamics simulations, the different variant ribosome translocation conformational trajectories are described. This description reveals different possible conformational pathways to translocation, with varying dynamics, motions and intermediates. The understanding of this conformational malleability can increase our knowledge of protein synthesis function, disruption, evolution, and engineering.
Citation
Alejo JL, Girodat D, Hammerling MJ, Willi JA, Jewett MC, Engelhart AE, et al. (2024) Alternate conformational trajectories in ribosome translocation. PLoS Comput Biol 20(8): e1012319. https://doi.org/10.1371/journal.pcbi.1012319
Supporting Information
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
Data Availability: The full next generation sequencing data for the various libraries employed in the Ribosome head domain hinge variant evolution are archived in the NIH National Library of Medicine - BioProject PRJNA1073529. The data from the molecular dynamics simulations are available at https://zenodo.org/records/11638475.