| Project/Area Number |
18H02389
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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 43020:Structural biochemistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
Arimori Takao 大阪大学, 蛋白質研究所, 准教授 (80582064)
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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 |
¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | 結晶構造解析 / クライオ電子顕微鏡 / 細胞接着 / 細胞外マトリックス |
|---|
| Outline of Final Research Achievements |
Recognition of laminin, a major component of the basement membrane, by integrin receptors plays a central role in the adhesion of epithelial cells to basement membrane, but the structural background of this molecular interaction has been unclear. In this study, we determined the three-dimensional structure of the laminin-integrin complex and elucidated its molecular recognition mechanism.
By using the previously developed antibody fragment, Fv-clasp, we succeeded in preparing a stable laminin-integrin complex sample and determined its structure at 3.9 Å-resolution by single particle cryo-electron microscopy. In addition, binding analysis using mutants of amino acid residues found at the binding interface revealed by the complex structure quantitatively clarified the contribution of each amino acid residue to the binding.
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| Academic Significance and Societal Importance of the Research Achievements |
インテグリンとラミニンの結合は細胞接着の足場として働くだけでなく，細胞の増殖や分化，生存などをコントロールしており，癌細胞においては浸潤や転移にも関与している．また，ES細胞やiPS細胞といった多能性幹細胞ではインテグリンが高発現しており，これらを培養する際には，ラミニンが接着培養の土台（培養基質）として実際に応用されている．本研究で詳細に明らかにしたインテグリンとラミニンの相互作用機構は，単なる生命現象の理解にとどまらず，創薬や再生医療にも大きく貢献するものである．
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