Cell Reports (Mar 2017)
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 Hustak,
- Florian Stengel,
- Eddie Dagraca,
- Asokan Ananbandam,
- Philip Gao,
- Takeshi Urano,
- Alan G. Hinnebusch,
- Gerhard Wagner,
- Katsura Asano
Affiliations
- Eiji Obayashi
- Shimane University School of Medicine, Izumo, Shimane 690-8504, Japan
- Rafael E. Luna
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
- Takashi Nagata
- Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011, Japan
- Pilar Martin-Marcos
- 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
- Hiroyuki Hiraishi
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Chingakham Ranjit Singh
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Jan Peter Erzberger
- Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
- Fan Zhang
- 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
- Haribabu Arthanari
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
- Jacob Morris
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Riccardo Pellarin
- California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA
- Chelsea Moore
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Ian Harmon
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Evangelos Papadopoulos
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
- Hisashi Yoshida
- Graduate School of Medical Life Science, Yokohama City University, Tsurumi-ku, Yokohama 230-0045, Japan
- Mahmoud L. Nasr
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
- Satoru Unzai
- Graduate School of Medical Life Science, Yokohama City University, Tsurumi-ku, Yokohama 230-0045, Japan
- Brytteny Thompson
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Eric Aube
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Samantha Hustak
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- Florian Stengel
- Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland
- Eddie Dagraca
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
- Asokan Ananbandam
- COBRE-PSF, University of Kansas, Lawrence, KS 66047, USA
- Philip Gao
- COBRE-PSF, University of Kansas, Lawrence, KS 66047, USA
- Takeshi Urano
- Shimane University School of Medicine, Izumo, Shimane 690-8504, Japan
- Alan G. Hinnebusch
- 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
- Gerhard Wagner
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
- Katsura Asano
- Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
- DOI
- https://doi.org/10.1016/j.celrep.2017.02.052
- Journal volume & issue
-
Vol. 18,
no. 11
pp. 2651 – 2663
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.
Keywords
- translation initiation
- ribosome
- eIF5
- eIF3
- eIF1
- start codon selection
- ribosomal pre-initiation complex
