Asymmetric dynamics of hetero dimeric ABC transporters explored by molecular simulations
| Project/Area Number |
15K00400
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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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| Research Field |
Life / Health / Medical informatics
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
Furuta Tadaomi 東京工業大学, 生命理工学院, 助教 (10431834)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ABCトランスポーター / ATP / 基質 / 輸送 / 変異 / 構造機能相関 / 疎水性クラスター / 分子シミュレーション / CFTR / ホモ・ヘテロ / 構造ダイナミクス |
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| Outline of Final Research Achievements |
ATP-binding cassette (ABC) transporters constitute a large superfamily of membrane proteins that transport various substrates through membranes utilizing the energy of ATP. In this study, we investigated asymmetric dynamics of ABC transporters TM287/288 and CFTR induced by the binding of ATP and substrate using molecular simulations. It was revealed that substrate binding induced allosteric interdomain communication in TM287 / 288 and that the most frequent mutation in CFTR caused the disruption of a hydrophobic cluster at the domain interface, leading to dysfunction. These findings would provide important insights into the structure-function relationship of ABC transporters.
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| Academic Significance and Societal Importance of the Research Achievements |
ABCトランスポーターおよびその変異は、多剤耐性や様々な疾患に関連している。本研究で得られたABCトランスポーターの構造ダイナミクスに関する重要な知見は、今後の創薬において揺らぎといった観点からも大変有益であると思われる。
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Report
(5 results)
Research Products
(33 results)
