Obayashi, E.Luna, R. E.Nagata, T.Martin-Marcos, P.Hiraishi, H.Singh, Chingakham RanjitErzberger, 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.Hustak, S.Stengel, F.Dagraca, E.Ananbandam, A.Gao, P.Urano, T.Hinnebusch, A. G.Wagner, G.Asano, Katsura2017-11-302017-11-30http://hdl.handle.net/2097/38323Citation: Obayashi, E., Luna, R. E., Nagata, T., Martin-Marcos, P., Hiraishi, H., Singh, C. R., . . . 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. doi:10.1016/j.celrep.2017.02.052During 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.Attribution 4.0 International (CC BY 4.0)https://creativecommons.org/licenses/by/4.0/Eukaryotic Translation InitiationStart-Codon RecognitionSelectionIn-VivoC-Terminal DomainPreinitiation ComplexArticle