| Project Area | Frontier research of chemical communications |
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| Project/Area Number |
17H06406
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Osaka University |
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Principal Investigator |
Murata Michio 大阪大学, 理学研究科, 教授 (40183652)
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| Co-Investigator(Kenkyū-buntansha) |
土川 博史 大分大学, 医学部, 特任講師 (30460992)
此木 敬一 東北大学, 農学研究科, 准教授 (40292825)
山下 まり 東北大学, 農学研究科, 教授 (50192430)
西川 俊夫 名古屋大学, 生命農学研究科, 教授 (90208158)
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| Project Period (FY) |
2017-06-30 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥76,180,000 (Direct Cost: ¥58,600,000、Indirect Cost: ¥17,580,000)
Fiscal Year 2021: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2020: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2019: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2018: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2017: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
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| Keywords | 天然物リガンド / 化学コミュニケーション / イオンチャネル / 脂質二重膜 / 細胞膜作動性リガンド / 膜貫通ドメイン / ATPアーゼ阻害剤 / ＡＴＰアーゼ / ATPアーゼ |
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| Outline of Final Research Achievements |
In this study, the interactions between membrane proteins and natural product ligands were elucidated by physicochemical and structural biology methods. Many marine natural products are known to act specifically on ion channels, etc. We aimed to elucidate the biological significance of these natural products, biosynthesis, structure-activity relationships, and, for biotoxins, mechanisms of action, and achieved our objectives by using exploration, isolation, structure determination, chemical biology, and electrophysiological methods. We were able to achieve our objectives through exploration, isolation, structure determination, chemical biology, and electrophysiological methods. The structure of amphotericin B, a historically known example of a natural product that forms ion channels by self-association in lipid bilayers, was determined at atomic resolution.
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| Academic Significance and Societal Importance of the Research Achievements |
天然リガンドの作用機構の解明や構造生物学的知見は、歴史的にも大変重要視されてきた。特に、海洋性生物毒が示す強力で特異的な阻害機構によって、幾多の画期的成果が生化学分野にもたらされている。一例を挙げると、フグ毒テトロドトキシンや下痢性貝毒オカダ酸によって、ナトリウムチャネルやタンパク質リン酸加水分解酵素の研究が進むことによって生物学や医薬学の進展が図られたように大きな波及効果を生む。従って、本研究で取り上げたイオンチャネルなどの膜タンパク質に結合する天然リガンドの研究成果は、特に創薬において有用な基礎的情報となる可能性がある。
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