Structural basis for the functional mechanism of eukaryotic initiation factor eIF2

• Project/Area Number: 23687013
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: The Institute of Physical and Chemical Research (2012-2014); The University of Tokyo (2011)
• Principal Investigator: ITO Takuhiro 独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, ユニットリーダー (70401164)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2011: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: 翻訳 / 翻訳開始因子 / eIF2 / eIF2B / X線結晶構造解析 / Ｘ線結晶構造解析

Outline of Final Research Achievements

We have determined the 3D structure of eukaryotic initiation factor 2B (eIF2B), which functions as a guanine nucleotide exchange factor specific for eIF2. Furthermore, we determined the eIF2-recognition regions in eIF2B. We identified more than two interaction modes between eIF2 and eIF2, and successfully proposed the structural model how phosphorylated eIF2 inhibits the GEF activity of eIF2B.
We determined the WD-repeat domain of eIF2A, which revealed that the domain possesses nine beta propellers.
We also determined the ternary complex of TrmD, tRNA, and AdoMet analog, which revealed the detailed molecular mechanism of the substrate tRNA recognition.

Research Products

• [Journal Article] Crystal structure of the eukaryotic translation initiation factor 2A from Schizosaccharomyces pombe (2014)
  • Author(s): Kazuhiro Kashiwagi, Takuhiro Ito, Shigeyuki Yokoyama
  • Journal Title: Journal of Structural and Functional Genomics Volume: - Issue: 3 Pages: 125-130
  • DOI: 10.1007/s10969-014-9177-y
  • Peer Reviewed
• [Presentation] Structural insight into the interaction between eIF2B and eIF2B (2014)
  • Author(s): Kashiwagi Kazuhiro, Takuhiro Ito, and Shigeyuki Yokoyama
  • Organizer: Translational Control 2014 in Cold Spring Harbor Laboratory
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2014-09-02
• [Presentation] Structural Structural insight into the eIF2-eIF2B interaction (2014)
  • Author(s): Kashiwagi Kazuhiro, Takuhiro Ito, and Shigeyuki Yokoyama
  • Organizer: 23rd Congress and General Assembly of the International Union of Crystallography
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2014-08-11
  • Invited
• [Presentation] Structural mechanism of site-specific RNA modification by the bacterial tRNA(m1G37)-methyltransferase TrmD (2013)
  • Author(s): Ito, T., Masuda, I., Yoshida, KI., Goto-ito, S., Sekine, SI., Wonsuh, S., Hou, YM. and Yokoyama, S.
  • Organizer: 7th International Conference on Structural Genomics 2013 - Structural Life Science (ICSG2013-SLS)
  • Place of Presentation: 札幌
• [Presentation] Structural basis of the sequence-specific methyltransfer reaction by bacterial tRNA methyltransferase TrmD (2013)
  • Author(s): Ito, T., Masuda, I., Yoshida, KI., Goto-ito, S., Sekine, SI., Wonsuh, S., Hou, YM. and Yokoyama, S.
  • Organizer: The 65th Fujihara Seminar International Symposium on Synthetic Biology of Unnatural Base Pairs and Amino Acids
  • Place of Presentation: 苫小牧
• [Presentation] Crystal Structure of the α subunit of human eukaryotic initiation factor 2B (2011)
  • Author(s): Takuya B Hiyama
  • Organizer: RNA2011 (16^<th> Annual meeting of the RNA society/第13回日本RNA学会年会)
  • Place of Presentation: 京都
  • Year and Date: 2011-06-17
• [Remarks] 翻訳因子構造解析研究ユニット
  • URL: http://www.riken.jp/research/labs/clst/struct_synth_biol/struct_biol/transl_fact_struct_biol/