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

By Amédée des Georges, Vidya Dhote, L. Kuhn, C. Hellen, T. Pestova, Joachim Frank, Y. Hashem. 2015

257 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

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Citations in the corpus

Structural Insights into the Mechanism of Scanning and Start Codon Recognition in Eukaryotic Translation Initiation. (2017, methodology): “Integrating information about meIF3 subunits in the PCI/MPN core that interact with eIF4G (3e/3c/3d) [76,77] and DHRC data identifying eIF4G middle domain (eIF4Gm) interactions with expansion segment 6 near the bottom of the 40S [78], the eIF4Gm and adjacent eIF3 binding domain were tentatively posi”
The Jigsaw Puzzle of mRNA Translation Initiation in Eukaryotes: A Decade of Structures Unraveling the Mechanics of the Process (2018, methodology): “The displayed eIF3 structure is a model derived from an ~6-Å cryo-EM map of the mammalian 43S preinitiation complex (30), which was in part interpreted thanks to the high-resolution structures of eIF3 fragments.”
Protein Synthesis Initiation in Eukaryotic Cells. (2018, background): “2, left) (des Georges et al. 2015) or alternatively the “peripheral” subunits (Simonetti et al. 2016).”
Long-range interdomain communications in eIF5B regulate GTP hydrolysis and translation initiation (2020, background): “Some of these proteins are also integrated into massive protein complexes, like the initiation factor eIF3 (5, 6).”
Structural Insights into the Mammalian Late-Stage Initiation Complexes (2020, methodology): “Because of its location, it is tempting to attribute this unassigned density to the 50 UTR of mRNA, but its presence in 43S PIC (des Georges et al., 2015), which does not contain any mRNA, strongly contradicts this assignment.”
A structural inventory of native ribosomal ABCE1‐43S pre‐initiation complexes (2020, unknown): “The PCI-MPN core is located at the backside of the 40S as observed before (des Georges et al , 2015; Hashem et al , 2013; Srivastava et al , 1992), and high S4), thus refining previous low-resolution models (des Georges et al , 2015; Eliseev et al , 2018; Erzberger et al , 2014), for example, by…”