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Analysis of the mechanism of protein aggregation at an atomic level and development of a method of stabilizing it by chemical modification

Research Project

Project/Area Number 25440069
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biophysics
Research InstitutionYokohama City University (2014-2016)
Osaka University (2013)

Principal Investigator

Ikegami Takahisa  横浜市立大学, 生命医科学研究科, 教授 (20283939)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords核磁気共鳴 / 蛋白質 / 立体構造解析 / 非特異的相互作用 / NMR / 凝集 / 疎水的相互作用 / 安定性 / 単分散 / 磁気緩和速度 / 緩和分散
Outline of Final Research Achievements

There are many examples of proteins interacting with each other while maintaining their specific three-dimensional structures, and leading to aggregation. Such aggregation is also associated with many kinds of diseases. It is also one of the causes that hinder detailed spectroscopic analyses such as NMR. The purpose of this study is to study the physical mechanism by which such aggregation occurs spontaneously and to develop chemical modification methods that inhibit it. I have targeted VanX, an enzyme involved in vancomycin resistance in Enterococci. The tertiary structure as a dimer was analyzed mainly by NMR. As a result, it was shown that VanX aggregates to tetramers as the concentration increases. It was also found that the degree of aggregation changes depending on the solvent pH.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015 2014 2013

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] The cyanobacterial cytochrome b6f subunit PetP adopts an SH3 fold in solution.2016

    • Author(s)
      Veit S, Nagadoi A, Roegner M, Rexroth S, Stoll R, Ikegami T.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1857 Issue: 6 Pages: 705-714

    • DOI

      10.1016/j.bbabio.2016.03.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Functional conformer of c-Myb DNA-binding domain revealed by variable temperature studies.2015

    • Author(s)
      Inaba S, Maeno A, Sakurai K, Narayanan SP, Ikegami T, Akasaka K, Oda M.
    • Journal Title

      FEBS J.

      Volume: 282 Issue: 23 Pages: 4497-4514

    • DOI

      10.1111/febs.13508

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intrinsic disorder mediates cooperative signal transduction in STIM12014

    • Author(s)
      Furukawa, Y., Teraguchi, S., Ikegami, T., Dagliyan, O., Jin, L., Hall, D., Dokholyan, N.V., Namba, K., Akira, S., Kurosaki, T., Baba, Y., Standley, D.M.
    • Journal Title

      J Mol Biol

      Volume: 426 Issue: 10 Pages: 2082-97

    • DOI

      10.1016/j.jmb.2014.03.006

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extraction of recombinantprotein from E.coli by using a novel cell autolysis activity of VanX2013

    • Author(s)
      Kamioka T, Sohya S, Wu N, Maki T, Matsuda T, Ikegami T, Nakamura H, Kuroda Y
    • Journal Title

      Analytical Biochemistry

      Volume: (in press) Issue: 2 Pages: 212-217

    • DOI

      10.1016/j.ab.2013.04.007

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] NMR spin-relaxation analyses of larger molecules2017

    • Author(s)
      池上貴久
    • Organizer
      RRR workshop 2017 Kyoto
    • Place of Presentation
      京都大学桂船井哲良記念講堂(京都府京都市)
    • Year and Date
      2017-02-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cooperativity observed in a signal transduction-related protein2016

    • Author(s)
      池上貴久
    • Organizer
      The 5th International Symposium on Drug Discovery and Design by NMR
    • Place of Presentation
      理研横浜交流棟(神奈川県横浜市鶴見区)
    • Year and Date
      2016-08-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysis of Artifacts Derived from Pulse Imperfections in CPMG Pulse Trains2016

    • Author(s)
      池上貴久
    • Organizer
      The XXVIIth International Conference on Magnetic Resonance in Biological Systems
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Book] 直積演算子(プロダクトオペレータ)の覚え方 in NMR 学会誌 72016

    • Author(s)
      長土居有隆、池上貴久
    • Total Pages
      130
    • Publisher
      日本核磁気共鳴学会
    • Related Report
      2016 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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