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Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome.

Priyanka D Abeyrathne | Cha San Koh | Timothy Grant | Nikolaus Grigorieff | Andrei A Korostelev
eLife | 2016

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.

Pubmed ID: 27159452

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: P01 GM062580
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM106105
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM107465
  • Agency: Howard Hughes Medical Institute, United States

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