Structures and assembly mechanisms of the molecular bushing allowing high-speed rotation of the bacterial flagellar motor

• Project/Area Number: 17K07318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Okinawa Institute of Science and Technology Graduate University (2018-2020); Institute of Physical and Chemical Research (2017)
• Principal Investigator: Matsunami Hideyuki 沖縄科学技術大学院大学, 生体分子電子顕微鏡解析ユニット, 研究員 (80444511)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細菌べん毛 / べん毛基部体 / 分子軸受け / Lリング / Pリング / シャペロン / ペリプラズム / X線結晶構造解析 / クライオ電子顕微鏡

Outline of Final Research Achievements

The molecular bushing composed of P-ring and L-ring locates at the cell surface and allows the high-speed rotation of the bacterial flagellum. FlgI, a component protein of P-ring, is exported to the periplasmic space in the cell surface through not the flagellar specific export system but the Sec export pathway and, then forms a binary complex with FlgA to stabilize before the P-ring assembly occurs. Moderately conserved hydrophobic residues in the C-terminal domain of FlgA involve the specific recognition of the C-terminal domain of FlgI by molecular mechanisms of preventing from self-assembly of FlgI.

Academic Significance and Societal Importance of the Research Achievements

ヒトや動物などに感染する病原性細菌が自由に動き回ることを抑制するためには、選択的にべん毛の構築を阻止することが有効である。そのためには、病原性細菌のべん毛が自己構築する仕組みを分子レベルで明らかにすることが極めて重要である。そこで、べん毛の分子軸受けができる仕組みについて詳しく理解することに着目して研究を行った。この研究成果をさらに発展させることで、病原性細菌を殺すことなくべん毛の構築を選択的に阻害する薬剤の開発に繋がることが期待される。

Research Products

• [Journal Article] Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome. (2020)
  • Author(s): Yoshimasa Takizawa, Cheng-Han Ho, Hiroaki Tachiwana, Hideyuki Matsunami, Wataru Kobayashi, Midori Suzuki, Yasuhiro Arimura, Tetsuya Hori, Tatsuo Fukagawa, Melanie D Ohi, Matthias Wolf, Hitoshi Kurumizaka
  • Journal Title: Structure Volume: 28 Issue: 1 Pages: 44-53
  • DOI: 10.1016/j.str.2019.10.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Architecture of the Bacterial Flagellar Distal Rod and Hook of Salmonella. (2019)
  • Author(s): Saijo-Hamano Y, Matsunami H, Namba K, Imada K
  • Journal Title: Biomolecules Volume: 9 Issue: 7 Pages: 260-260
  • DOI: 10.3390/biom9070260
  • Peer Reviewed / Open Access
• [Journal Article] Torque transmission mechanism of the curved bacterial flagellar hook revealed by cryo-EM. (2019)
  • Author(s): Shibata S, Matsunami H, Aizawa SI, Wolf M
  • Journal Title: Nature structural & molecular biology Volume: 26 Issue: 10 Pages: 941-945
  • DOI: 10.1038/s41594-019-0301-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evidence for the hook supercoiling mechanism of the bacterial flagellum (2018)
  • Author(s): Takashi Fujii,Hideyuki Matsunami, Yumi Inoue and Keiichi Namba
  • Journal Title: Biophysics and Physicobiology Volume: 15 Issue: 0 Pages: 28-32
  • DOI: 10.2142/biophysico.15.0_28
  • NAID: 130006337975
  • ISSN: 2189-4779
  • Peer Reviewed / Open Access
• [Journal Article] Cryo-EM Structure of Campylobacter Flagellar Hook (2017)
  • Author(s): 松波秀行
  • Journal Title: Seibutsu Butsuri Volume: 57 Issue: 5 Pages: 265-267
  • DOI: 10.2142/biophys.57.265
  • NAID: 130006100202
  • ISSN: 0582-4052, 1347-4219
  • Peer Reviewed / Open Access