Conformational Differences between Open and Closed States of the Eukaryotic Translation Initiation Complex

Jose L. Llácer, Tanweer Hussain, Laura Marler, Colin Echeverría Aitken, Anil Thakur, Jon R. Lorsch, Alan G. Hinnebusch, V. Ramakrishnan

Research output: Contribution to journalArticle

Abstract

Translation initiation in eukaryotes begins with the formation of a pre-initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and eIF5. The PIC, in an open conformation, attaches to the 5' end of the mRNA and scans to locate the start codon, whereupon it closes to arrest scanning. We present single particle cryo-electron microscopy (cryo-EM) reconstructions of 48S PICs from yeast in these open and closed states, at 6.0Å and 4.9Å, respectively. These reconstructions show eIF2β as well as a configuration of eIF3 that appears to encircle the 40S, occupying part of the subunit interface. Comparison of the complexes reveals a large conformational change in the 40S head from an open mRNA latch conformation to a closed one that constricts the mRNA entry channel and narrows the P site to enclose tRNAi, thus elucidating key events in start codon recognition.

Original languageEnglish (US)
Pages (from-to)399-412
Number of pages14
JournalMolecular cell
Volume59
Issue number3
DOIs
StatePublished - Aug 6 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Llácer, J. L., Hussain, T., Marler, L., Aitken, C. E., Thakur, A., Lorsch, J. R., Hinnebusch, A. G., & Ramakrishnan, V. (2015). Conformational Differences between Open and Closed States of the Eukaryotic Translation Initiation Complex. Molecular cell, 59(3), 399-412. https://doi.org/10.1016/j.molcel.2015.06.033