| Project/Area Number |
18K06199
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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 43060:System genome science-related
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| Research Institution | Tokyo Denki University |
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Principal Investigator |
Nemoto Wataru 東京電機大学, 理工学部, 准教授 (10455438)
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| Co-Investigator(Kenkyū-buntansha) |
藤 博幸 関西学院大学, 理工学部, 教授 (70192656)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | GPCRs / タンパク質間相互作用 / 相互作用ペア予測 / 疾患関連変異 / 機械学習 / 膜タンパク質 / Autoencoder / インターフェイス / GPCR / 変異 / 疾患 / 相互作用 / 予測 |
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| Outline of Final Research Achievements |
We have previously developed GGIP, a method to predict GPCR-interaction pairs with high accuracy. In this study, we propose a workflow to predict disease-associated mutations to GPCRs that affect GPCR oligomerizations. The rhodopsin mutants F45L, V209M and F220C, which are known to cause retinitis pigmentosa by inhibiting rhodopsin dimer formation, were predicted to be interaction inhibitive mutations. Similarly, the A707T mutation in GB1, which has been suggested to be associated with Rett syndrome and inhibits heterodimer formation with GB2, was also predicted to be an interaction inhibitive mutation. A same strategy was applied to cancer-causing mutations. The application of the strategy to cancer-causing mutations showed that the number of interaction inhibitive mutations was larger than that of interaction promotive mutations.
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| Academic Significance and Societal Importance of the Research Achievements |
変異導入前後での予測結果を比較する本研究は、変異が分子機能変化を通して形質変化に至る機構を議論する汎用的手法に拡張可能である。短時間で変異の影響を見積もるため、任意のタンパク質の全残基を変異させ影響を予測するなどの網羅的解析が可能で、蓄積し続ける変異情報の解析基盤に発展する。表現型の個人差を生む遺伝情報の差異の解析と分子機構解明は、医薬開発への貢献が考えられる。サイトカイン・ストームやブラジキニン・ストームに関与するGPCRsは、他の膜タンパク質との相互作用、相互作用モチーフ、機能変化が報告されており、COVID-19含むウイルス研究との関連でも興味深い
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