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Structural analysis of various light-driven reaction mechanisms of light-sensitive proteins.

Planned Research

Project AreaNon-equilibrium-state molecular movies and their applications
Project/Area Number 19H05779
Research Category

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

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionYokohama City University

Principal Investigator

Park SamYong  横浜市立大学, 生命医科学研究科, 教授 (20291932)

Co-Investigator(Kenkyū-buntansha) 梅名 泰史  名古屋大学, シンクロトロン光研究センター, 准教授 (10468267)
別所 義隆  国立研究開発法人理化学研究所, 放射光科学研究センター, 客員研究員 (70242815)
Project Period (FY) 2019-06-28 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥106,470,000 (Direct Cost: ¥81,900,000、Indirect Cost: ¥24,570,000)
Fiscal Year 2023: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2022: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2021: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2020: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥42,120,000 (Direct Cost: ¥32,400,000、Indirect Cost: ¥9,720,000)
KeywordscGMP光産生酵素 / 光反応酵素 / X線自由電子レーザー / 光感受性タンパク質 / 時分割解析
Outline of Research at the Start

光によって感応・応答するタンパク質には、動物や植物などに広く分布する発色団を含み、生命維持に関与するなど重要な役割を果たすものが知られる。近年では、こうした光感受性タンパク質を利用して、細胞などの光操作する技術に応用され(光遺伝学)、これまでに多くの生理現象の解明に利用されてきた。本研究計画では、疾病治療への利用が期待されている、またはツールとしての重要性が高いとされる光感受性タンパク質について、XFELを用いた高速分子動画実験を行うことで、タンパク質内部で起こる光エネルギー移動や高速な構造変化について明らかにする。

Outline of Final Research Achievements

Since the static structure of the light-sensitive adenylate cyclase (OaPAC) was already known from single crystals, we sought to improve the crystallization conditions for the preparation of microcrystals. X-ray diffraction experiments at room temperature at the Swiss Light Source revealed crystals floating on a film in the ultrasonic range with a resolution of 2.2-2.4 A. The results of the analysis showed that the BLUF domain was not affected by the crystallization conditions. The analysis showed that the movement of flavin and the neighboring residue Gln48 in the BLUF domain were observed to approach each other, and that the movement of Gln48 was completed after 3 seconds.

Academic Significance and Societal Importance of the Research Achievements

光によって感応、応答するタンパク質には、動物や植物などに広く分布する発色団を含み、生命維持に関与するなど重要な役割を果たすものが知られる。近年では、こうした光感受性タンパク質を利用して、細胞などの光操作する技術に応用され、これまでに多くの生理現象の解明に利用されてきた。中でも、光遺伝学は、細胞や組織の生理機能を明らかにするための非常に強力な研究手法であると同時に、疾病の治療への応用の観点からも注目されている。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (11 results)

All 2023 2022 2021 2020 2018

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Structural basis of CXC chemokine receptor 1 ligand binding and activation2023

    • Author(s)
      Ishimoto Naito、Park Jae-Hyun、Kawakami Kouki、Tajiri Michiko、Mizutani Kenji、Akashi Satoko、Tame Jeremy R. H.、Inoue Asuka、Park Sam-Yong
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 4107-4107

    • DOI

      10.1038/s41467-023-39799-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 22023

    • Author(s)
      Park Jae-Hyun、Kawakami Kouki、Ishimoto Naito、Ikuta Tatsuya、Ohki Mio、Ekimoto Toru、Ikeguchi Mitsunori、Lee Dong-Sun、Lee Young-Ho、Tame Jeremy R. H.、Inoue Asuka、Park Sam-Yong
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 7150-7150

    • DOI

      10.1038/s41467-023-42764-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface2022

    • Author(s)
      Heo Yunseok、Ishimoto Naito、Jeon Ye-Eun、Yun Ji-Hye、Ohki Mio、Anraku Yuki、Sasaki Mina、Kita Shunsuke、Fukuhara Hideo、Ikuta Tatsuya、Kawakami Kouki、Inoue Asuka、Maenaka Katsumi、Tame Jeremy R. H.、Lee Weontae、Park Sam-Yong
    • Journal Title

      PLOS Biology

      Volume: 20 Issue: 8 Pages: e3001714-e3001714

    • DOI

      10.1371/journal.pbio.3001714

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural insights into the HBV receptor and bile acid transporter NTCP2022

    • Author(s)
      Park JH, Iwamoto M, Yun JH, Uchikubo-Kamo T, Son D, Jin Z, Yoshida H, Ohki M, Ishimoto N, Mizutani K, Oshima M, Muramatsu M, Wakita T, Shirouzu M, Liu K, Uemura T, Nomura N, Iwata S, Watashi K, Tame JRH, Nishizawa T, Lee W, Park SY.
    • Journal Title

      Nature

      Volume: 606 Issue: 7916 Pages: 1027-1031

    • DOI

      10.1038/s41586-022-04857-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Leucine-sensing mechanism of leucyl-tRNA synthetase 1 for mTORC1 activation.2021

    • Author(s)
      Kim S, Yoon I, Son J, Park J, Kim K, Lee JH, Park SY, Kang BS, Han JM, Hwang KY, Kim S.
    • Journal Title

      Cell Rep.

      Volume: 35(4) Issue: 4 Pages: 1-13

    • DOI

      10.1016/j.celrep.2021.109031

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early-stage dynamics of chloride ion-pumping rhodopsin revealed by a femtosecond X-ray laser.2021

    • Author(s)
      MS, Liang M, Sierra RG, Lane TJ, Zhou L, Weierstall U, Zatsepin NA, Ohki M, Tame JRH, Park SY, Spence JCH, Zhang W, Schmidt M, Lee W, Liu H.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 118(13) Issue: 13 Pages: 1-9

    • DOI

      10.1073/pnas.2020486118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure- Based Functional Modification Study of a Cyanobacterial Chloride Pump for Transporting Multiple Anions.2020

    • Author(s)
      Yun JH, Park JH, Jin Z, Ohki M, Wang Y, Lupala CS, Liu H, Park SY*, Lee W*
    • Journal Title

      J Mol Biol

      Volume: 432 Issue: 19 Pages: 5273-5286

    • DOI

      10.1016/j.jmb.2020.07.016

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct observation of ligand migration within human hemoglobin at work2020

    • Author(s)
      Shibayama Naoya、Sato-Tomita Ayana、Ohki Mio、Ichiyanagi Kouhei、Park Sam-Yong
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 9 Pages: 4741-4748

    • DOI

      10.1073/pnas.1913663117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pumping mechanism of NM-R3, a light-driven bacterial chloride importer in the rhodopsin family2020

    • Author(s)
      Yun Ji-Hye、Ohki Mio、Park Jae-Hyun、Ishimoto Naito、Sato-Tomita Ayana、Lee Wonbin、Jin Zeyu、Tame Jeremy R. H.、Shibayama Naoya、Park Sam-Yong、Lee Weontae
    • Journal Title

      Science Advances

      Volume: 6 Issue: 6 Pages: 6-6

    • DOI

      10.1126/sciadv.aay2042

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Non-cryogenic structure of a chloride pump provides crucial clues to temperature-dependent channel transport efficiency2018

    • Author(s)
      Yun Ji-Hye、Li Xuanxuan、Park Jae-Hyun、Wang Yang、Ohki Mio、Jin Zeyu、Lee Wonbin、Park Sam-Yong、Hu Hao、Li Chufeng、Zatsepin Nadia、Hunter Mark S.、Sierra Raymond G.、Koralek Jake、Yoon Chun Hong、Cho Hyun-Soo、Weierstall Uwe、Tang Leihan、Liu Haiguang、Lee Weontae
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 3 Pages: 794-804

    • DOI

      10.1074/jbc.ra118.004038

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 光活性化アデニル酸シクラーゼの構造生物学的考察2020

    • Author(s)
      大木 規央、富田 文菜、松永 茂、伊関 峰生、テイム ジェレミー、柴山 修哉、朴 三用
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Annual Research Report
    • Invited

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Published: 2019-07-04   Modified: 2025-01-30  

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