Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5 - Institut Pasteur Access content directly
Journal Articles Cell Reports Year : 2017

Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5

Eiji Obayashi
  • Function : Author
Rafael Luna
  • Function : Author
Takashi Nagata
  • Function : Author
Pilar Martin-Marcos
  • Function : Author
Hiroyuki Hiraishi
  • Function : Author
Chingakham Ranjit Singh
  • Function : Author
Jan Peter Erzberger
  • Function : Author
Fan Zhang
  • Function : Author
  • PersonId : 1005688
Haribabu Arthanari
  • Function : Author
Jacob Morris
  • Function : Author
Chelsea Moore
  • Function : Author
Ian Harmon
  • Function : Author
Evangelos Papadopoulos
  • Function : Author
Hisashi Yoshida
  • Function : Author
Mahmoud Nasr
  • Function : Author
Satoru Unzai
  • Function : Author
Brytteny Thompson
  • Function : Author
Eric Aube
  • Function : Author
Samantha Hustak
  • Function : Author
Eddie Dagraca
  • Function : Author
Asokan Ananbandam
  • Function : Author
Philip Gao
  • Function : Author
Takeshi Urano
  • Function : Author
Alan Hinnebusch
  • Function : Author
Gerhard Wagner
  • Function : Author

Abstract

During eukaryotic translation initiation, eIF3 binds the solvent-accessible side of the 40S ribosome and recruits the gate-keeper protein eIF1 and eIF5 to the decoding center. This is largely mediated by the N-terminal domain (NTD) of eIF3c, which can be divided into three parts: 3c0, 3c1, and 3c2. The N-terminal part, 3c0, binds eIF5 strongly but only weakly to the ribosome-binding surface of eIF1, whereas 3c1 and 3c2 form a stoichiometric complex with eIF1. 3c1 contacts eIF1 through Arg-53 and Leu-96, while 3c2 faces 40S protein uS15/S13, to anchor eIF1 to the scanning pre-initiation complex (PIC). We propose that the 3c0:eIF1 interaction diminishes eIF1 binding to the 40S, whereas 3c0:eIF5 interaction stabilizes the scanning PIC by precluding this inhibitory interaction. Upon start codon recognition, interactions involving eIF5, and ultimately 3c0:eIF1 association, facilitate eIF1 release. Our results reveal intricate molecular interactions within the PIC, programmed for rapid scanning-arrest at the start codon.
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pasteur-02406441 , version 1 (12-12-2019)

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Eiji Obayashi, Rafael Luna, Takashi Nagata, Pilar Martin-Marcos, Hiroyuki Hiraishi, et al.. Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5. Cell Reports, 2017, 18 (11), pp.2651-2663. ⟨10.1016/j.celrep.2017.02.052⟩. ⟨pasteur-02406441⟩

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