Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyRNA Therapeutics Institute
Document Type
Journal ArticlePublication Date
2016-05-09Keywords
IRESS. cerevisiae
Taura syndrome virus
biochemistry
biophysics
elongation factor eEF2
internal ribosome entry site
ribosome
structural biology
translocation
Biochemistry
Biophysics
Structural Biology
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Show full item recordAbstract
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.Source
Elife. 2016 May 9;5. pii: e14874. doi: 10.7554/eLife.14874. Link to article on publisher's site
DOI
10.7554/eLife.14874Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40035PubMed ID
27159452Related Resources
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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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.14874
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Except where otherwise noted, this item's license is described as 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.