| Project/Area Number |
18H02413
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
Park Sam-Yong 横浜市立大学, 生命医科学研究科, 教授 (20291932)
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| Co-Investigator(Kenkyū-buntansha) |
小山 隆太 東京大学, 大学院薬学系研究科(薬学部), 准教授 (90431890)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2018: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | 光活性化アデニル酸シクラーゼ / 光反応酵素 / 光遺伝学 / 構造解析 / アデニル酸シクラーゼ / 構造生物学 |
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| Outline of Final Research Achievements |
Optogenetics is a rapidly growing field in which light is used to control biological systems. We show that OaPAC protein produces the fundamental second messenger cyclic-AMP (cAMP) in response to blue light, is stable and functional in human cells, and can therefore be used to trigger events by raising cAMP level. OaPAC consists of a catalytic domain controlled by a photosensitive BLUF domain. We have solved the crystal structure to show how activity is triggered by light, and guide mutagenesis experiments. Although the catalytic domain resembles known cyclases, the BLUF domains form an unusual intertwined structure. The protein activity is the same in solution as in the crystal, showing that the activation mechanism involves only very small molecular movements.
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| Academic Significance and Societal Importance of the Research Achievements |
青光により活性化アデニル酸シクラーゼcAMP分子を量産する酵素として、特性解明や生物機能光制御への展開も提唱・実行してきた。本申請者は、PACの相同遺伝子であるOaPACの立体構造解明に世界初めて成功し、光活性化機構に関する構造科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。神経興奮の光制御、いわゆる光遺伝学、が急速に普及し、OaPACによるcAMPを介する生体機能光制御も概念上同類とみなされつつあるが、はるかに広範で多彩な生命活動の光制御につながり、血管新生・脳病変原生・神経回路ネットワーキング・記憶などの光発生医学現象の制御・解明・治療・創薬スクリーニング開拓を先導するものである。
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