Alteration of antigen recognition and structural dynamics of antibodies during affinity maturation
| Project/Area Number |
18K06161
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Kyoto Prefectural University |
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Principal Investigator |
Oda Masayuki 京都府立大学, 生命環境科学研究科, 教授 (20318231)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 抗体 / 抗原結合 / 安定性 / 結晶構造 / 分子認識 |
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| Outline of Final Research Achievements |
Single-chain Fv (scFv) antibodies against nitrophenyl (NP) on the process of affinity maturation were generated, and their structural, functional, and physical properties were analyzed. The X-ray crystal structure of NP complexed with C6 scFv, affinity-matured type, was determined, showing the structural basis of molecular recognition. The change in thermal stability was analyzed for the scFvs possessing Gly at residue 95 of heavy chain. The stability of germline-type scFv was higher than that of affinity-matured type, which was increased upon NP binding.
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| Academic Significance and Societal Importance of the Research Achievements |
生体内での抗体の親和性成熟の構造基盤を解明し、如何に抗原結合能を高めるかといった抗体医薬分野へも応用可能な知見を得た。また抗体の抗原結合能と熱安定性がトレードオフ関係にあることを示し、蛋白質科学的な抗体の理解のみならず、免疫学的な意義、すなわち抗原結合前の不安定化は結合後の安定化で補われるという知見を得て、今後の蛋白質ラショナルデザイン全般に活かされる。
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Report
(4 results)
Research Products
(10 results)
