| Project/Area Number |
18K06077
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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 43020:Structural biochemistry-related
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
Toma-Fukai Sachiko 奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (40363535)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | X線結晶構造解析 / ユビキチン / ユビキチンE3リガーゼ / 構造生物学 / 結晶構造解析 / ユビキチンリガーゼ / 構造生物 / Ｘ線結晶構造解析 / ポリユビキチン化反応 / 翻訳後修飾酵素 / 創薬 |
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| Outline of Final Research Achievements |
Hepatic gluconeogenesis is an issue in patients with type 2 diabetes, but the details of the signaling mechanism are unknown. The expression of genes in the glycogenic enzyme group causes glycogenesis. Previously it was reported that histone acetyltransferase GCN5 is one of the enzymes involved in hepatic glycogenesis, but the full extent of this mechanism has not been clarified.
GCN5 has a domain presumed to have ubiquitin E3 activity, named PCAF_N. We focused our structural studies on a novel catalytic activity, E3 activity, of GCN5, an acetyltransferase involved in glycogenesis. As a result, we revealed that PCAF_N is an E3 enzyme with a novel fold.
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| Academic Significance and Societal Importance of the Research Achievements |
アセチル化やユビキチン化は蛋白質合成後に起こる翻訳後修飾である。シグナル伝達において翻訳後修飾は互いに競合または協調しながら多様な情報を伝える。本研究では、GCN5のE3活性機構の解明はGCN5が分解シグナルを誘導するという全く新しい機能を立体構造から解明した。これは、GCN分子が持つ未知シグナル伝達の可能性を示し、GCN5が担う糖新生シグナルの解明に貢献する学術的意義、社会的意義のある研究成果である。
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