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Mol Cell. 2015 Aug 6;59(3):399-412. doi: 10.1016/j.molcel.2015.06.033. Epub 2015 Jul 23.

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

Author information

1
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
2
Laboratory of Gene Regulation and Development, Eunice K. Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
3
Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice K. Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
4
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address: ramak@mrc-lmb.cam.ac.uk.

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 6.0 Å and 4.9 Å, 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.

PMID:
26212456
PMCID:
PMC4534855
DOI:
10.1016/j.molcel.2015.06.033
[Indexed for MEDLINE]
Free PMC Article

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