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

Cell Reports

Philip Gao¹  Asokan Ananbandam¹  Riccardo Pellarin²  Gerhard Wagner³  Eddie Dagraca³  Rafael E. Luna³  Haribabu Arthanari³  Mahmoud L. Nasr³  Evangelos Papadopoulos³  Jan Peter Erzberger⁴  Florian Stengel⁵  Hisashi Yoshida⁶  Satoru Unzai⁶  Takashi Nagata⁷  Alan G. Hinnebusch⁸  Fan Zhang⁸  Pilar Martin-Marcos⁸  Jacob Morris⁹  Chelsea Moore⁹  Brytteny Thompson⁹  Hiroyuki Hiraishi⁹  Chingakham Ranjit Singh⁹  Katsura Asano⁹  Samantha Hustak⁹  Ian Harmon⁹  Eric Aube⁹  Eiji Obayashi^1,10  Takeshi Urano^1,10 

[1] COBRE-PSF, University of Kansas, Lawrence, KS 66047, USA;California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA;Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA;Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland;Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland;Graduate School of Medical Life Science, Yokohama City University, Tsurumi-ku, Yokohama 230-0045, Japan;Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011, Japan;Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA;Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA;Shimane University School of Medicine, Izumo, Shimane 690-8504, Japan;

关键词: translation initiation;    ribosome;    eIF5;    eIF3;    eIF1;    start codon selection;    ribosomal pre-initiation complex;   

DOI  :  10.1016/j.celrep.2017.02.052

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown