Analysis of heme-dependent degradation mechanisms of ALAS1, mitochondrial heme synthesis enzyme
| Project/Area Number |
18K06116
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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 43030:Functional biochemistry-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
古山 和道 岩手医科大学, 医学部, 教授 (80280874)
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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 |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | ヘム / タンパク質分解 / ミトコンドリア / ヘム生合成経路 / プロテアーゼ / ヘム合成 |
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| Outline of Final Research Achievements |
Heme is an important molecule that contains iron atoms and binds to various proteins to regulate their functions, but excess heme causes oxidative damage to DNA and proteins. Therefore, regulation of heme biosynthesis is important for living organisms. We have found that aminolevulinic acid synthase, the enzyme that catalyze the first step of heme synthesis pathway, is degraded in a heme-dependent manner. In this study, we elucidated part of the recognition mechanism of heme-bound aminolevulinic acid synthase by the specific protease.
The recognition by the protease was found to be mediated by a 90-amino acid region outside the catalytic domain of aminolevulinic acid synthase. Furthermore, it was suggested that this region contains a degradation-promoting domain and an inhibitory domain, and that heme binding to the degradation-promoting domain weakens the inhibition by the inhibitory domain, resulting in recognition by the degrading enzyme.
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| Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリアに存在するアミノレブリン酸合成酵素には、酵素活性を持つ触媒領域以外に90アミノ酸からなる分解酵素認識配列が存在することを初めて見出した。この配列を任意のタンパク質に融合させると、ヘムを投与することによってこのタンパク質の分解を誘導することが可能である。この発見により、ミトコンドリアにおけるタンパク質分解を制御できるツールが得られたと言える。
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Report
(4 results)
Research Products
(2 results)
