Structure-guided functional analysis of membrane proteins for human iron absorption using living cells
| Project/Area Number |
18K05321
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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 37010:Bio-related chemistry
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| Research Institution | University of Hyogo |
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Principal Investigator |
Sawai Hitomi 兵庫県立大学, 生命理学研究科, 助教 (50584851)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 鉄代謝 / 鉄還元酵素 / 鉄イオンの吸収 / ヒト腸管モデル細胞 / ヘム / 金属トランスポーター / ヘム酵素 / Ｘ線結晶構造解析 / 構造機能相関 / Caco-2-kh細胞 / 膜タンパク質 / 構造機能解析 / 鉄吸収 |
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| Outline of Final Research Achievements |
Iron obtained from the diet are reduced by the transmembrane ferric reductase Dcytb, which is located in the cell membrane on the intestinal lumen side of duodenal enterocytes. The reduced iron is then transported into the enterocytes by the divalent metal ion transporter DMT1. In this project, some functional evaluation systems using living cells were established to investigate the structure-function relations of human Dcytb and to screen dietary ingredients for improvement of iron absorption. Those results indicated that the C-terminal region of Dcytb is related to the regulation of iron absorption and transport. In addition, supplementation of fructose and malic acid improved the efficiency of iron absorption. If the detailed molecular mechanisms of these new findings at the cellular-level studies are revealed, it will help improve the safety and efficiency of orally administered nutritional iron agents in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
鉄は、生命維持に必須の微量金属元素である。しかし、過剰な鉄の蓄積は活性酸素源となるため、生体内の鉄は厳密に制御されている。ヒトには制御可能な鉄の排出経路がないため、鉄の吸収調節が最も重要な過程になる。食物に含まれる鉄イオンは、十二指腸粘膜上皮細胞に局在する膜タンパク質Dcytb/DMT1の働きにより腸管から細胞内に吸収されるため、これらの機能不全は疾病の原因となる。本研究では、Dcytbの立体構造に基づく情報を生きた細胞で検証することにより、ヒトの鉄イオン吸収機構を詳細に解明することを目指した。この成果は将来的に、鉄栄養素の効率的な摂取方法や鉄代謝異常による疾病の理解につながる。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate.2018
Author(s)
Ganasen M, Togashi H, Takeda H, Asakura H, Tosha T, Yamashita K, Hirata K, Nariai Y, Urano T, Yuan X, Hamza I, Mauk AG, Shiro Y, Sugimoto H, Sawai H.
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Journal Title
Communications Biology
Volume: 1
Issue: 1
Pages: 120-120
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Architecture of a Complete Two-Component Signal Transduction System: Oxygen-Sensing Proteins FixL, FixJ, and Their Complex2018
Author(s)
G. S. A. Wright, A. Saeki, T. Hikima, Y. Nishizono, T. Hisano, M. Yamamoto, S. V. Antonyuk, S. S. Hasnain, Y. Shiro, H. Sawai
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Journal Title
Sci. Signal.
Volume: 11
Issue: 525
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Book] NTS出版2021
Author(s)
城宜嗣、澤井仁美、當舍武彦
Total Pages
13
Publisher
生命金属のダイナミクス
Related Report
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