2022 Fiscal Year Final Research Report
Unnatural amino acid-based state-specific analysis of ion channels
| Project/Area Number |
20K07284
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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 48020:Physiology-related
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| Research Institution | National Institute for Physiological Sciences |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | イオンチャネル / 電位依存性 / 非天然アミノ酸 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop and demonstrate a method to "target" a specific state by introducing a photocrosslinking unnatural amino acid (pcUAA) into an ion channel. Several pcUAA-introduced mutants of the S4 helix in the voltage sensor domain of Kv1.2, a voltage-gated potassium channel, were irradiated with UV light simultaneously with current measurements to observe changes in channel activity. Some of the pcUAA-introduced mutants were found to be more sensitive to cross-link formation when the S4 helix was in a resting state. This result provided a new insight into the mechanism of channel activation in voltage-gated ion channel.
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| Free Research Field |
生物物理学
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| Academic Significance and Societal Importance of the Research Achievements |
Kv1.2を含む電位依存性イオンチャネルは、われわれの脳や末梢神経における電気信号を生み出す基本単位であり、その分子機能・構造についての理解は生理学的に重要である。本研究の結果、Kv1.2のS4ヘリックスの構造変化についての知見が得られた。構造解析技術の発展にもかかわらず、高分解能のKv1.2の静止状態の構造は明確に得られておらず、電位依存的な活性化メカニズムは完全には理解されていない。pcUAAを利用した本研究の結果は、その活性化メカニズムについての新しい知見を提供するものである。
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