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Molecular mechanism of photoactivation of a light-regulated adenylate cyclase in cell

Research Project

Project/Area Number 17K15076
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionYokohama City University

Principal Investigator

Ohki Mio  横浜市立大学, 生命医科学研究科, 特任助教 (10791361)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords光遺伝学 / 構造生物学 / 光活性化アデニル酸シクラーぜ / 構造解析 / セカンドメッセンジャー
Outline of Final Research Achievements

Optogenetics is a rapidly growing field in which light is used to control biological systems. We show that Oscillatoria acuminata photoactivated adenylate cyclase (OaPAC) protein produces the fundamental second messenger cyclic-AMP (cAMP) in response to blue light, is stable and functional in different mammalian cell types, and can be used to trigger events by raising cAMP level. OaPAC consists of a catalytic domain controlled by a photosensitive blue light using flavin (BLUF) domain. We have solved the crystal structure.Based on structural elucidation of the OaPAC activate mechanism, application development of light control second messenger in cells, development of cGMP production enzyme by adenylate cyclase domain modification and aiming for basic medical research to medical treatment such as neural circuit formation disease by optogenetics.

Academic Significance and Societal Importance of the Research Achievements

光活性化アデニル酸シクラーゼ(PAC)は特性解明や生物機能光制御への展開も提唱・実行されており、また藍藻由来のPACである、OaPACの立体構造解明に成功し、光活性化機構に関する構造生物学的な研究は本研究グループが先駆的に積み上げてきた。
近年、「光遺伝学」が急速に普及し、OaPACによるcAMPを介する生体機能光制御は、光発生医学現象の制御・解明・治療・創薬スクリーニングという広大な新分野の開拓を先導かつ独創的な新領域の研究分野であると言える。本研究により今後、構造生命科学的解析を基盤として、優れた特性の改良型OaPACの創出とそれに基づく広範で多彩な応用展開につながることが期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results)

  • [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
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction.2018

    • Author(s)
      Saso W, Tsukuda S, Ohashi H, Fukano K, Morishita R, Matsunaga S, Ohki M, Ryo A, Park SY, Suzuki R, Aizaki H, Muramatsu M, Sureau C, Wakita T, Matano T, Watashi K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 印刷中 Issue: 2 Pages: 374-379

    • DOI

      10.1016/j.bbrc.2018.04.187

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular mechanism of photoactivation of a light-regulated adenylate cyclase2017

    • Author(s)
      Ohki Mio、Sato-Tomita Ayana、Matsunaga Shigeru、Iseki Mineo、Tame Jeremy R. H.、Shibayama Naoya、Park Sam-Yong
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 114 Issue: 32 Pages: 8562-8567

    • DOI

      10.1073/pnas.1704391114

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 光活性化cyclicAMP合成酵素PACの構造生物学2017

    • Author(s)
      大木規央、伊関 峰生、朴 三用
    • Organizer
      2017年度 酵素補酵素研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 光活性化cyclicAMP合成酵素PACの構造生物学2017

    • Author(s)
      大木規央、柴山 修哉、松永 茂、朴 三用
    • Organizer
      2017年度 生命科学系学会合同年次学会大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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