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

Eiji Obayashi, Rafael E. Luna, Takashi Nagata, Pilar Martin-Marcos, Hiroyuki Hiraishi, Chingakham Ranjit Singh, Jan Peter Erzberger, Fan Zhang, Haribabu Arthanari, Jacob Morris, Riccardo Pellarin, Chelsea Moore, Ian Harmon, Evangelos Papadopoulos, Hisashi Yoshida, Mahmoud L. Nasr, Satoru Unzai, Brytteny Thompson, Eric Aube, Samantha HustakFlorian Stengel, Eddie Dagraca, Asokan Ananbandam, Philip Gao, Takeshi Urano, Alan G. Hinnebusch, Gerhard Wagner, Katsura Asano

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2651-2663
Number of pages13
JournalCell Reports
Volume18
Issue number11
DOIs
StatePublished - Mar 14 2017

Keywords

  • eIF1
  • eIF3
  • eIF5
  • ribosomal pre-initiation complex
  • ribosome
  • start codon selection
  • translation initiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Obayashi, E., Luna, R. E., Nagata, T., Martin-Marcos, P., Hiraishi, H., Singh, C. R., Erzberger, J. P., Zhang, F., Arthanari, H., Morris, J., Pellarin, R., Moore, C., Harmon, I., Papadopoulos, E., Yoshida, H., Nasr, M. L., Unzai, S., Thompson, B., Aube, E., ... Asano, K. (2017). Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5. Cell Reports, 18(11), 2651-2663. https://doi.org/10.1016/j.celrep.2017.02.052