Work

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

Year: 2016

Type: article

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.

Source: eLife

DOI: 10.7554/elife.14874

Authors: Priyanka D Abeyrathne, Cha San Koh, Timothy Grant, Nikolaus Grigorieff, Andrei A Korostelev

Institutions: Howard Hughes Medical Institute, Janelia Research Campus, University of Massachusetts Chan Medical School

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,500

Funders: Howard Hughes Medical Institute, National Institutes of Health, National Institute of General Medical Sciences