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Structural and functional analysis of tripartite ABC transporter MacB

Research Project

Project/Area Number 18K06079
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionTokyo Institute of Technology

Principal Investigator

Okada Ui  東京工業大学, 生命理工学院, 助教 (20507181)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords構造生物化学 / X線結晶構造解析 / ABC輸送体 / 膜蛋白質 / 薬剤耐性 / 構造生物学 / 輸送タンパク質 / X線結晶解析 / 膜輸送体
Outline of Final Research Achievements

The macrolide efflux transporter MacB is a member of ATP-binding cassette (ABC) transporter which forms a tripartite efflux complex with a membrane fusion protein MacA and an outer membrane channel TolC. The molecular mechanism of the substrate translocation by MacAB-TolC complex remains largely unknown. We determined the first crystal structure of MacB from Acinetobacter baumannii at 3.4 angstrom resolution in 2017. In this study, we have determined the higher resolution structure of MacB homolog at 2.0 angstrom resolution, and several structures from other conditions have also been solved. The structural comparison between these structures revealed the conformational change of MacB, and these results provide new insights into the mechanism of the substrate translocation.

Academic Significance and Societal Importance of the Research Achievements

本研究の対象であるMacBは、マクロライド系抗生物質やペプチド毒素、リポ多糖等の生物学的に重要な物質の排出に関与しており、その排出機構を解明することは、創薬のみならず生命現象の理解という観点からも非常に有用な情報が引き出せると期待される。本研究で明らかとなったMacBの構造変化は、従来のABC輸送体とは大きく異なるものであった。これらの結果から、詳細が解明されていないMacBを含むVII型ABC輸送体の基質輸送の分子機構について、新たなモデルを提唱した。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae2021

    • Author(s)
      Bharatham Nagakumar、Bhowmik Purnendu、Aoki Maho、Okada Ui、Sharma Sreevalli、Yamashita Eiki、Shanbhag Anirudh P.、Rajagopal Sreenath、Thomas Teby、Sarma Maitrayee、Narjari Riya、Nagaraj Savitha、Ramachandran Vasanthi、Katagihallimath Nainesh、Datta Santanu、Murakami Satoshi
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41467-021-25679-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 三者複合体形成型ABCトランスポーターMacBの構造解析2020

    • Author(s)
      岡田 有意、村上 聡
    • Journal Title

      Farumashia

      Volume: 56 Issue: 6 Pages: 499-503

    • DOI

      10.14894/faruawpsj.56.6_499

    • NAID

      130007850168

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tripartite transporters as mechanotransmitters in periplasmic alternating-access mechanisms.2020

    • Author(s)
      Murakami, Okada, van Veen
    • Journal Title

      FEBS Letters

      Volume: 594 Issue: 23 Pages: 3908-3919

    • DOI

      10.1002/1873-3468.13929

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Acta Crystallogr. F

      Volume: 74 Issue: 11 Pages: 710-716

    • DOI

      10.1107/s2053230x18013547

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii2021

    • Author(s)
      Okada Ui
    • Organizer
      PDB50 Anniversary Symposium in Asia
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii2019

    • Author(s)
      Ui Okada, Eiki Yamashita, Arthur Neuberger, Mayu Morimoto, Hendrik W. van Veen & Satoshi Murakami
    • Organizer
      Gordon Research Conference on Multi-Drug Efflux Systems
    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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