Crossref journal-article
eLife Sciences Publications, Ltd
eLife (4374)
Abstract

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.

Bibliography

Abeyrathne, P. D., Koh, C. S., Grant, T., Grigorieff, N., & Korostelev, A. A. (2016). Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome. ELife, 5. CLOCKSS.

Authors 5
  1. Priyanka D Abeyrathne (first)
  2. Cha San Koh (additional)
  3. Timothy Grant (additional)
  4. Nikolaus Grigorieff (additional)
  5. Andrei A Korostelev (additional)
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Dates
Type When
Created 9 years, 3 months ago (May 9, 2016, 7:59 a.m.)
Deposited 1 year, 10 months ago (Oct. 11, 2023, 8:50 p.m.)
Indexed 3 weeks, 6 days ago (July 30, 2025, 1:08 p.m.)
Issued 9 years, 3 months ago (May 9, 2016)
Published 9 years, 3 months ago (May 9, 2016)
Published Online 9 years, 3 months ago (May 9, 2016)
Funders 4
  1. National Institutes of Health 10.13039/100000002

    Region: Americas

    gov (National government)

    Labels3
    1. Institutos Nacionales de la Salud
    2. US National Institutes of Health
    3. NIH
    Awards1
    1. GM62580
  2. Howard Hughes Medical Institute 10.13039/100000011

    Region: Americas

    pri (Research institutes and centers)

    Labels2
    1. Howard Hughes Medical Institute Inc
    2. HHMI
  3. National Institutes of Health 10.13039/100000002

    Region: Americas

    gov (National government)

    Labels3
    1. Institutos Nacionales de la Salud
    2. US National Institutes of Health
    3. NIH
    Awards1
    1. GM106105
  4. National Institutes of Health 10.13039/100000002

    Region: Americas

    gov (National government)

    Labels3
    1. Institutos Nacionales de la Salud
    2. US National Institutes of Health
    3. NIH
    Awards1
    1. GM107465

@article{Abeyrathne_2016, title={Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome}, volume={5}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.14874}, DOI={10.7554/elife.14874}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Abeyrathne, Priyanka D and Koh, Cha San and Grant, Timothy and Grigorieff, Nikolaus and Korostelev, Andrei A}, year={2016}, month=may }