Laboratory for Translation Structural Biology

Research Summary

We study three dimensional structures of the translation factors and/or the ribosome, mainly by X-ray crystallography and cryo-EM. We focus on the structural analysis of the large complexes that function in the eukaryotic translational system, in order to reveal the complicated mechanisms of eukaryotic translation.

Crystal structure of S. pombe eIF2B

Cryo-EM structures of human eIF2-eIF2B complexes

Research Theme

• Structural biology on translational system in eukaryotes
• Development of the sample preparation methods suitable for the crystallization/cryo-EM analysis of macromolecular complexes

Main Publications List

• Zyryanova AF, Kashiwagi K, Rato C, et al.
  ISRIB blunts the integrated stress response by allosterically antagonising the inhibitory effect of phosphorylated eIF2 on eIF2B.
  Molecular Cell 81. 88-103 (2021) doi: 10.1016/j.molcel.2020.10.031
• Yokoyama T, Machida K, Iwasaki W, et al.
  HCV IRES Captures an Actively Translating 80S Ribosome.
  Molecular Cell 74. 1205-1214 (2019) doi: 10.1016/j.molcel.2019.04.022
• Kashiwagi K, Yokoyama T, Nishimoto M, et al.
  Structural basis for eIF2B inhibition in integrated stress response.
  Science 364. 495-499 (2019) doi: 10.1126/science.aaw4104
• Iwasaki S, Iwasaki W, Takahashi M, et.al.
  The translation inhibitor Rocaglamide targets a bimolecular cavity between eIF4A and polypurine RNA.
  Molecular Cell 73. 738-748 (2019) doi: 10.1016/j.molcel.2018.11.026
• Kashiwagi K, Takahashi M, Nishimoto M, et al.
  Crystal structure of eukaryotic translation initiation factor 2B.
  Nature 531. 122-125 (2016) doi: 10.1038/nature16991
• Ito T., Masuda I., Yoshida K., et al.
  Structural Basis for methyl-donor-dependent and sequence-specific binding to tRNA substrates by knotted methyltransferase TrmD.
  Proceedings of the National Academy of Sciences of the United States of America 112. E4197-E4205 (2015) doi: 10.1073/pnas.1422981112
• Ito T, Yokoyama S.
  Two enzymes bound to one transfer RNA assume alternative conformations for consecutive reactions.
  Nature 467. 612-616 (2010) doi: 10.1038/nature09411
• Goto-Ito S, Ito T, Kuratani M, et al.
  Tertiary structure checkpoint at anticodon loop modification in tRNA functional maturation.
  Nature Structural & Molecular Biology 16. 1109-1115 (2009) doi: 10.1038/nsmb.1653

All Publications

Member

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• 2019/08/09 Research How phosphorylation of eIF2 reduces protein synthesis
• 2019/03/08 Research Natural plant defense could lead to new personalized cancer therapy