| 研究課題/領域番号 |
21K15036
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分43030:機能生物化学関連
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| 研究機関 | 東北大学 |
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研究代表者 |
張 玉霞 東北大学, 多元物質科学研究所, 助教 (10899769)
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| 研究期間 (年度) |
2021-04-01 – 2022-03-31
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| 研究課題ステータス |
中途終了 (2021年度)
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| 配分額 *注記 |
4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円)
2022年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
2021年度: 2,470千円 (直接経費: 1,900千円、間接経費: 570千円)
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| キーワード | cryo-EM / SERCA2b / Calcium pump |
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| 研究開始時の研究の概要 |
Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) 2b pumps Ca2+ from the cytosol into the ER and maintains the cellular calcium homeostasis. We study on the structures and function of SERCA2b by high-end cryo-EM to comprehensively understand the mechanism of SERCA2b. We propose a new ATP entry pathway into its binding pocket based on our current new cryo-EM structure of SERCA2b in E12Ca2+ state. Besides, to gain deeper insight into SERCA2b under more physiological condition, we also plan to treat SERCA2b with ATP and explore the structural dynamics of SERCA2b by time-resolved cryo-EM analysis.
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| 研究実績の概要 |
We newly determined several cryo-EM structures of SERCA2b, including a high-energy E1P state with two bound Ca ions and the post-E1P state immediately after Ca release. The dataset in E2P state identified a new conformation that differs from the conventional E2P state and the subsequent E2-Pi state that can be regarded as a late-stage Ca-unbound intermediate. The cryo-EM structures suggested that SERCA2b adopts multiple conformations in reaction and generates preformed states closely resembling the next intermediate. These findings provide essential structural insight into how enzymes work; multiple sub-states, including one highly similar to a next intermediate, are formed in a reaction intermediate to facilitate the transition step and thereby drive the catalytic cycle efficiently.
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