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Nature. 2015 Sep 24;525(7570):491-5. doi: 10.1038/nature14891. Epub 2015 Sep 7.

Structure of mammalian eIF3 in the context of the 43S preinitiation complex.

Author information

1
HHMI, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
2
Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA.
3
CNRS, Proteomic Platform Strasbourg - Esplanade, Strasbourg 67084, France.
4
Department of Biological Sciences, Columbia University, New York, New York 10032, USA.
5
CNRS, Architecture et Réactivité de l'ARN, Université de Strasbourg, Strasbourg 67084, France.

Abstract

During eukaryotic translation initiation, 43S complexes, comprising a 40S ribosomal subunit, initiator transfer RNA and initiation factors (eIF) 2, 3, 1 and 1A, attach to the 5'-terminal region of messenger RNA and scan along it to the initiation codon. Scanning on structured mRNAs also requires the DExH-box protein DHX29. Mammalian eIF3 contains 13 subunits and participates in nearly all steps of translation initiation. Eight subunits having PCI (proteasome, COP9 signalosome, eIF3) or MPN (Mpr1, Pad1, amino-terminal) domains constitute the structural core of eIF3, to which five peripheral subunits are flexibly linked. Here we present a cryo-electron microscopy structure of eIF3 in the context of the DHX29-bound 43S complex, showing the PCI/MPN core at ∼6 Å resolution. It reveals the organization of the individual subunits and their interactions with components of the 43S complex. We were able to build near-complete polyalanine-level models of the eIF3 PCI/MPN core and of two peripheral subunits. The implications for understanding mRNA ribosomal attachment and scanning are discussed.

PMID:
26344199
PMCID:
PMC4719162
DOI:
10.1038/nature14891
[Indexed for MEDLINE]
Free PMC Article

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