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Dynamics of uS19 C-Terminal Tail during the Translation Elongation Cycle in Human Ribosomes

Abstract : Ribosomes undergo multiple conformational transitions during translation elongation. Here, we report the high-resolution cryoelectron microscopy (cryo-EM) structure of the human 80S ribosome in the post-decoding pre-translocation state (classical-PRE) at 3.3-Å resolution along with the rotated (hybrid-PRE) and the post-translocation states (POST). The classical-PRE state ribosome structure reveals a previously unobserved interaction between the C-terminal region of the conserved ribosomal protein uS19 and the A- and P-site tRNAs and the mRNA in the decoding site. In addition to changes in the inter-subunit bridges, analysis of different ribosomal conformations reveals the dynamic nature of this domain and suggests a role in tRNA accommodation and translocation during elongation. Furthermore, we show that disease-associated mutations in uS19 result in increased frameshifting. Together, this structure-function analysis provides mechanistic insights into the role of the uS19 C-terminal tail in the context of mammalian ribosomes.
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https://www.hal.inserm.fr/inserm-03103230
Contributor : Bruno Klaholz <>
Submitted on : Friday, January 8, 2021 - 7:30:15 AM
Last modification on : Saturday, January 9, 2021 - 3:30:13 AM
Long-term archiving on: : Friday, April 9, 2021 - 6:15:21 PM

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Varun Bhaskar, Alexandra Graff-Meyer, Andreas Schenk, Simone Cavadini, Ottilie von Loeffelholz, et al.. Dynamics of uS19 C-Terminal Tail during the Translation Elongation Cycle in Human Ribosomes. Cell Reports, Elsevier Inc, 2020, 31 (1), pp.107473. ⟨10.1016/j.celrep.2020.03.037⟩. ⟨inserm-03103230⟩

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