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

Author

Listed:
  • Amedee des Georges

    (HHMI, Columbia University)

  • Vidya Dhote

    (SUNY Downstate Medical Center)

  • Lauriane Kuhn

    (CNRS)

  • Christopher U. T. Hellen

    (SUNY Downstate Medical Center)

  • Tatyana V. Pestova

    (SUNY Downstate Medical Center)

  • Joachim Frank

    (HHMI, Columbia University
    Columbia University)

  • Yaser Hashem

    (CNRS, Architecture et Réactivité de l’ARN, Université de Strasbourg)

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.

Suggested Citation

  • Amedee des Georges & Vidya Dhote & Lauriane Kuhn & Christopher U. T. Hellen & Tatyana V. Pestova & Joachim Frank & Yaser Hashem, 2015. "Structure of mammalian eIF3 in the context of the 43S preinitiation complex," Nature, Nature, vol. 525(7570), pages 491-495, September.
    • Handle: RePEc:nat:nature:v:525:y:2015:i:7570:d:10.1038_nature14891
    DOI: 10.1038/nature14891
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    Cited by:

    1. Huilin Jin & Xiaoling Huang & Qihao Pan & Ning Ma & Xiaoshan Xie & Yue Wei & Fenghai Yu & Weijie Wen & Boyu Zhang & Peng Zhang & Xijie Chen & Jie Wang & Ran-yi Liu & Junzhong Lin & Xiangqi Meng & Mong, 2024. "The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Yifei Gu & Yuanhui Mao & Longfei Jia & Leiming Dong & Shu-Bing Qian, 2021. "Bi-directional ribosome scanning controls the stringency of start codon selection," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. Bikash Chandra Swain & Pascale Sarkis & Vanessa Ung & Sabrina Rousseau & Laurent Fernandez & Ani Meltonyan & V. Esperance Aho & Davide Mercadante & Cameron D. Mackereth & Mikayel Aznauryan, 2024. "Disordered regions of human eIF4B orchestrate a dynamic self-association landscape," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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