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Structural basis for multimodal sensation in TRP channels

Research Project

Project/Area Number 18K06156
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43040:Biophysics-related
Research InstitutionTottori University

Principal Investigator

HINO Tomoya  鳥取大学, 工学研究科, 准教授 (40373360)

Co-Investigator(Kenkyū-buntansha) 西澤 知宏  東京大学, 大学院理学系研究科(理学部), 助教 (80599077)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsイオンチャネル / 膜タンパク質 / X線結晶構造解析 / クライオ電子顕微鏡 / 結晶化 / クライオ電顕 / TRPチャネル
Outline of Final Research Achievements

TRP channels are cation selective ion channels that respond not only to chemical stimuli such as pungent chemicals but also to physical stimuli including temperature changes, mechanical force, and osmotic pressure. In this study, we investigated the effect of PIP2, a lipid molecule known as a regulator of TRP channel activity, on the temperature responses. From the cryo-EM analysis, we successfully constructed atomic model of mouse TRPV3 and found that the lipid molecules are bound between the pore helix and S6 helix presumed to be involved in the channel activation process. We also found the conditions for the microcrystal formation of human TRPV3 for serial femto-second X-ray crystallography.

Academic Significance and Societal Importance of the Research Achievements

温度感知はほとんどの人が日常的に感じる極めて身近な生理現象である。本研究ではその感覚を引き起こす最初の段階を担うタンパク質であるTRPチャネルがどの様にして温度を感じ取るのかを原子レベルで明らかにしようという試みである。今回の結果は、脂質分子がTRPチャネルの活性化制御に重要な役割を果たすことを示唆しており、このタンパク質分子の結晶作成に成功したことも含め、今後分子レベルでの温度感知理解につながることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism2020

    • Author(s)
      Shimada Hiroto*、Kusakizako Tsukasa*、Dung Nguyen T. H.、Nishizawa Tomohiro、Hino Tomoya、Tominaga Makoto、Nureki Osamu (*equal contribution)
    • Journal Title

      Nature Structural & Molecular Biology

      Volume: 27 Issue: 7 Pages: 645-652

    • DOI

      10.1038/s41594-020-0439-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Applicability of Styrene-Maleic Acid Copolymer for Two Microbial Rhodopsins, RxR and HsSRI.2020

    • Author(s)
      Tetsuya Ueta, Keiichi Kojima, Tomoya Hino, Mikihiro Shibata, Shingo Nagano, Yuki Sudo*
    • Journal Title

      Biophysical journal

      Volume: 119 Issue: 9 Pages: 1760-1770

    • DOI

      10.1016/j.bpj.2020.09.026

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unique features of the ketosynthase domain in a nonribosomal peptide synthetase?polyketide synthase hybrid enzyme, tenuazonic acid synthetase 12020

    • Author(s)
      Yun Choong-Soo、Nishimoto Kazuki、Motoyama Takayuki、Shimizu Takeshi、Hino Tomoya、Dohmae Naoshi、Nagano Shingo、Osada Hiroyuki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 33 Pages: 11602-11612

    • DOI

      10.1074/jbc.ra120.013105

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] SFXによるTRPチャネルの熱刺激感知機構の解明に向けた微結晶試料の作製2020

    • Author(s)
      〇三坂 圭生,前田 朋輝,細川 航輔,永野 真吾,日野 智也
    • Organizer
      令和2年度新学術領域「高速分子動画」シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] TRPV3の微結晶品質をいかに向上させるか2020

    • Author(s)
      ◯日野智也
    • Organizer
      令和2年度新学術領域「高速分子動画」シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 結晶化に向けたヒト由来TRPV4変異体の構築2019

    • Author(s)
      細川航輔、前田朋輝、永野真吾、日野智也
    • Organizer
      第19回日本蛋白質科学会年会 第71回日本細胞生物学会大会 合同年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト由来TRPV3の精製及び結晶化2019

    • Author(s)
      前田朋輝、小島要、細川航輔、永野真吾、日野智也
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 温度感受性イオンチャネルhTRPV4の精製及び結晶化2019

    • Author(s)
      細川航輔、前田朋輝、野村弥生、佐藤有美、野村紀通、岩田想、永野真吾、日野智也
    • Organizer
      令和元年度結晶学会
    • Related Report
      2019 Research-status Report
  • [Presentation] TRPV3のnanodisc再構成における脂質添加量の影響2018

    • Author(s)
      前田朋輝、小島要、永野真吾、日野智也
    • Organizer
      第18回日本蛋白質科学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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