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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Codon, Initiator / genetics
  • Cryoelectron Microscopy
  • Eukaryotic Initiation Factor-2 / chemistry
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-3 / chemistry*
  • Eukaryotic Initiation Factor-3 / metabolism*
  • Humans
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / metabolism*
  • Peptide Chain Initiation, Translational*
  • Peptide Initiation Factors / metabolism
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • RNA Helicases / chemistry
  • RNA Helicases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Transfer, Met / metabolism
  • Ribosome Subunits, Small, Eukaryotic / chemistry
  • Ribosome Subunits, Small, Eukaryotic / metabolism
  • Ribosomes / chemistry*
  • Ribosomes / metabolism*

Substances

  • Codon, Initiator
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-3
  • Multiprotein Complexes
  • Peptide Initiation Factors
  • Protein Subunits
  • RNA, Messenger
  • RNA, Transfer, Met
  • DHX29 protein, human
  • RNA Helicases

Associated data

  • PDB/5A5T
  • PDB/5A5U