2021 Fiscal Year Final Research Report
Developement of technology for visualising lipid bilayers in crystals of membrane proteins
| Project/Area Number |
20K20376
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| Project/Area Number (Other) |
18H05367 (2018-2019)
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| Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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| Allocation Type | Multi-year Fund (2020)
Single-year Grants (2018-2019) |
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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
恒川 直樹 東京大学, 定量生命科学研究所, 特任研究員 (90638800)
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| Project Period (FY) |
2018-06-29 – 2022-03-31
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| Keywords | 脂質二重膜 / X線結晶解析 / 膜蛋白質 / 結晶 |
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| Outline of Final Research Achievements |
Aiming at a truly comprehensive structural biology of membrane proteins, we have been developing technology for visualizing all components, from protons to lipid bilayers, required for functioning of membrane proteins. Our first goal is to establish the methods for visualizing lipid bilayers in crystals of membrane proteins, or determining phases of reflections at lower than 10 Angstrom resolution. For that purpose, we designed X-ray solvent contrast modulation, multiple isomorphous replacements and their combinations, and carried out extensive measurements using crystals of ion pumps. Furthermore, we tried to develop methodology for generating larger crystals of membrane proteins aiming at the solvent contrast modulation using neutron diffraction.
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| Free Research Field |
構造生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果、低角反射に対する位相決定技術が拡充され、既に実績のある溶媒コントラスト変調法に関しても適用できる結晶が大幅に拡大した。その結果、これまでX線結晶解析が機能しないためにごく限られた知見しかない、燐脂質と膜蛋白質との相互作用の詳細を明らかにすることが可能になった他、蛋白質結晶中で熱運動が大きくて解像できなかった糖鎖等も解像できるようになった。クライオ電子顕微鏡法では燐脂質頭部が解像されないことが多いため、本研究で開発した技術との組み合わせも追及されるべきであろう
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