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生体膜の曲率・脂質パッキング状態変化を誘起する機能性ペプチド

Publicly Offered Research

Project AreaChemical Approaches for Miscellaneous / Crowding Live Systems
Project/Area Number 18H04547
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Research InstitutionKyoto University

Principal Investigator

二木 史朗  京都大学, 化学研究所, 教授 (50199402)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords細胞膜 / 脂質パッキング / 膜曲率 / 生体膜 / 曲率 / ペプチド
Outline of Annual Research Achievements

細胞膜は、種々の脂質、タンパク質、糖などが密集する究極の分子夾雑環境である。この分子夾雑環境の中で細胞膜と特異的に相互作用し、膜の形や脂質パッキング状態を制御できれば、細胞の運動、分化、分裂、融合などを制御する分子ツールが得られる。また、膜との相互作用を介して、膜に「担持」されたタンパク質(受容体など)の働きを調節できれば、直接的なタンパク質―タンパク質相互作用ではなく、タンパク質の置かれた「環境」を変えることで「細胞内イベント」を制御するユニークな分子ツールとなり得る。これらの分子ツールは、細胞・生体機能の解明を目的とする生命化学の基礎研究に対してのみならず、がん細胞の転移抑制、神経細胞やiPS細胞の分化調節など、医療応用に向けた展開も可能である。しかし、分子設計の困難さから、細胞膜の構造制御に向けた化学的アプローチは進んでいない。本研究では、「細胞膜という分子夾雑環境」で、膜曲率誘導・制御を通して「膜の形状や流動性、さらには膜に担持されたタンパク質の機能を制御するペプチド」を創出すると同時に、「新しい細胞操作技術としての生命化学分野における展開」を目指した。その結果として、(1)細胞表面への曲率誘導ペプチド集積化技術の開発と膜流動性の向上; (2)膜張力減弱能を併せ持つ曲率誘導ペプチドの開発と細胞運動、神経細胞形態への影響); (3)膜曲率関知ペプチドの開発 ;(4)ペプチドの多量化による曲率誘導能の向上に関しての成果を得た。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (15 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results)

  • [Int'l Joint Research] Karlsruhe Institute of Technology (KIT)(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Karlsruher Institut fur Technologie(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Enhancing the Activity of Membrane Remodeling Epsin-Peptide by Trimerization2020

    • Author(s)
      Wei-Yuan Hsu, Toshihiro Masuda, Sergii Afonin, Takayuki Sakai, Jan Vincent V. Arafiles, Kenichi Kawano, Hisaaki Hirose, Miki Imanishi, Anne S. Ulrich, Shiroh Futaki
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: - Issue: 12 Pages: 127190-127190

    • DOI

      10.1016/j.bmcl.2020.127190

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of a Membrane Curvature-Sensing Peptide Based on a Structure–Activity Correlation Study2019

    • Author(s)
      Kawano Kenichi、Ogushi Masaya、Masuda Toshihiro、Futaki Shiroh
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 10 Pages: 1131-1138

    • DOI

      10.1248/cpb.c19-00465

    • NAID

      130007721992

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-10-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loosening of Lipid Packing by Cell‐Surface Recruitment of Amphiphilic Peptides by Coiled‐Coil Tethering2019

    • Author(s)
      Sakai Takayuki、Kawano Kenichi、Iino Masatomo、Takeuchi Toshihide、Imanishi Miki、Futaki Shiroh
    • Journal Title

      ChemBioChem

      Volume: 20 Issue: 16 Pages: 2151-2159

    • DOI

      10.1002/cbic.201900347

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An influenza-derived membrane tension-modulating peptide regulates cell movement and morphology via actin remodeling2019

    • Author(s)
      Masuda Toshihiro、Baba Kentarou、Nomura Takeshi、Tsujita Kazuya、Murayama Tomo、Itoh Toshiki、Takatani-Nakase Tomoka、Sokabe Masahiro、Inagaki Naoyuki、Futaki Shiroh
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 243-243

    • DOI

      10.1038/s42003-019-0486-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 生体膜を標的とする機能性ペプチド:分子設計と作用機序2020

    • Author(s)
      二木史朗
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Modulating Lipid Packing of Cell Membranes for the Access to Cell Interiors2019

    • Author(s)
      Shiroh Futaki
    • Organizer
      Chemistry and Biology of Peptides 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 分子夾雑で細胞膜を制御する2019

    • Author(s)
      二木史朗
    • Organizer
      第9回CSJ化学フェスタ2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] An influenza-derived membrane tension-modulating peptide regulates cell movement and morphology via actin remodeling2019

    • Author(s)
      Shiroh Futaki
    • Organizer
      The Fourth A3 Roundtable Meeting on Chemical Probe Research Hub
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ペプチドを用いた細胞膜の構造・物性変換2018

    • Author(s)
      二木史朗
    • Organizer
      第91回日本生化学会大会 シンポジウム「生体膜の形態変化のメカニズム」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Structural determinants of membrane curvature inducing peptide2018

    • Author(s)
      Nishimura, M.; Masuda, T.; Kawano, K.; Futaki, S.
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Peptide to Modulate Membrane Tension: The Effect on Actin Organization, Cell Structure and the Movement2018

    • Author(s)
      Masuda, T.; Baba, K.; Murayama, T.; Inagaki, N.; Futaki, S.
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidating structural factors of curvature-inducing peptides2018

    • Author(s)
      Mishimura, M.; Pujals, S.; Murayama, T.; Kawano, K.; Futaki, S.
    • Organizer
      22nd Korean Peptide and Protein Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Approach to control cell movement by affecting membrane tension2018

    • Author(s)
      Masuda, T.; Murayama, T.; Futaki, S.
    • Organizer
      22nd Korean Peptide and Protein Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-01-27  

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