RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Biochemistry | Biophysics | Structural Biology
Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2*GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation.
IRES, S. cerevisiae, Taura syndrome virus, biochemistry, biophysics, elongation factor eEF2, internal ribosome entry site, ribosome, structural biology, translocation
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Copyright © 2016, Abeyrathne et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Elife. 2016 May 9;5. pii: e14874. doi: 10.7554/eLife.14874. Link to article on publisher's site
Abeyrathne PD, Koh CS, Grant T, Grigorieff N, Korostelev AA. (2016). Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome. Open Access Articles. https://doi.org/10.7554/eLife.14874. Retrieved from https://escholarship.umassmed.edu/oapubs/2841
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