Alternate conformational trajectories in ribosome translocation

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dc.contributor.authorAlejo, Jose L.
dc.contributor.authorGirodat, Dylan
dc.contributor.authorHammerling, Michael J.
dc.contributor.authorWilli, Jessica A.
dc.contributor.authorJewett, MIchael C.
dc.contributor.authorEngelhart, Aaron E.
dc.contributor.authorAdamala, Katarzyna P.
dc.date.accessioned2025-03-04T20:01:43Z
dc.date.available2025-03-04T20:01:43Z
dc.date.issued2024
dc.descriptionOpen access. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
dc.description.abstractTranslocation 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.
dc.description.peer-reviewYes
dc.identifier.citationAlejo, 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
dc.identifier.urihttps://hdl.handle.net/10133/7016
dc.language.isoen
dc.publisherPublic Library of Science
dc.publisher.departmentDepartment of Chemistry & Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Minnesota
dc.publisher.institutionUniversity of Arkansas
dc.publisher.institutionNorthwestern University
dc.publisher.institutionStanford University
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.urlhttps://doi.org/10.1371/journal.pcbi.1012319
dc.subjectRibosomes
dc.subjectTransfer RNA
dc.subjectRibosomal RNA
dc.subjectProtein synthesis
dc.subjectFree energy
dc.subjectVariant genotypes
dc.subjectBiochemical simulations
dc.subjectProtein translation
dc.subject.lcshProteins--Synthesis
dc.subject.lcshRibosomes--Research
dc.titleAlternate conformational trajectories in ribosome translocation
dc.typeArticle
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