1. Alternate conformational trajectories in ribosome translocation.
- Author
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Alejo JL, Girodat D, Hammerling MJ, Willi JA, Jewett MC, Engelhart AE, and Adamala KP
- Subjects
- Protein Biosynthesis, Nucleic Acid Conformation, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Messenger chemistry, Peptide Elongation Factor G metabolism, Peptide Elongation Factor G chemistry, Peptide Elongation Factor G genetics, Computational Biology, Ribosomes metabolism, Ribosomes chemistry, RNA, Transfer metabolism, RNA, Transfer chemistry, RNA, Transfer genetics, Molecular Dynamics Simulation
- 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alejo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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