Structural and Functional analysis on tripartite ABC transporters.
| Project/Area Number |
18H02386
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Tokyo Institute of Technology |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
成田 新一郎 山形県立米沢栄養大学, 健康栄養学部, 教授 (30338751)
徳田 元 盛岡大学, その他部局等, 名誉教授 (40125943)
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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 |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 構造生物学 / X線結晶構造解析 / 膜輸送 / 膜蛋白質 / 薬剤耐性 / ABC輸送体 / 薬剤排出 |
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| Outline of Final Research Achievements |
We solved a high-resolution crystal structure of MacB homolog. Compared to the published MacB structure, we observed several structural differences between them, especially around the transmembrane and the periplasmic domain. Comparison of these structures provides new insight on how substrates in the periplasm are captured and transported through the connecting pathway. In addition, we found that the substrate transport mechanism from the periplasmic space is similar to that of RND transporters, which we are studying separately. In view of the similarities and differences in substrate transport mechanisms, we proposed the “periplasmic alternating-access mechanism”. We also helped to propose a new classification of ABC transporters by the ABC transporter research society. And MacB is newly categolised as the type-VII ABC transporter.
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| Academic Significance and Societal Importance of the Research Achievements |
感染症は人間社会を一変させることを我々はここ1，2年で思い知った。ウイルス感染症に限らず、細菌感染症もまた脅威である。抗生物質はその有効性を徐々に失いつつある。ウイルスの陰で薬剤耐性菌が増えているという事実も報告され始めた。嫌なニュースである。抗生物質の能動的な排出の機構の理解は、輸送阻害剤の開発のほか、排出されにくい薬剤の設計にも利用可能な知見であり、人類の福祉にとって極めて重要な研究内容であると考える。基礎学問的にもどのようにしてグラム陰性細菌が斯くも多様なトランスポーターを分子進化のなかで保持してきたのかという興味に一歩近づけたと考えている。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] BpeB, a major resistance-nodulation-cell division transporter from Burkholderia cenocepacia: construct design, crystallization and preliminary structural analysis2018
Author(s)
T. Horikawa, L.-W. Hung, H.-B. Kim, D. Shaya, C.-Y. Kim, T. C. Terwilliger, E. Yamashita, M. Aoki, U. Okada and S. Murakami
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Journal Title
Acta Crystallogr. F
Volume: 74
Issue: 11
Pages: 710-716
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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