Alternate conformational trajectories in ribosome translocation
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Date
2024
Authors
Alejo, Jose L.
Girodat, Dylan
Hammerling, Michael J.
Willi, Jessica A.
Jewett, MIchael C.
Engelhart, Aaron E.
Adamala, Katarzyna P.
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
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.
Description
Open access. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
Keywords
Ribosomes , Transfer RNA , Ribosomal RNA , Protein synthesis , Free energy , Variant genotypes , Biochemical simulations , Protein translation
Citation
Alejo, J. L., Girodat, D., Hammerling, M. J., Willi, J. A., Jewett, M. C., Engelhard, A. E., & Adamala, K. P. (2024). Alternate conformational trajectories in ribosome translocation. PLoS Computational Biology, 20(8), Article e1012319. https://doi.org/10.1371/journal.pcbi.1012319