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Effects on p53 diffusion along dsDNA and nonspecific binding constant between p53 and dsDNA of hyper-mobile water control

Research Project

Project/Area Number 19K06576
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43040:Biophysics-related
Research InstitutionTohoku University

Principal Investigator

Suzuki Makoto  東北大学, 多元物質科学研究所, 名誉教授 (60282109)

Co-Investigator(Kenkyū-buntansha) 鎌形 清人  東北大学, 多元物質科学研究所, 准教授 (90432492)
最上 譲二  東北大学, 工学研究科, 助教 (70713022)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsDNAタンパク質相互作用 / DNA水和 / 誘電分光水和解析 / ラマン分光水和解析 / OH stretch band / cooperative vibration / 水分子間協同振動モード / ハイパーモバイル水 / DNA結合タンパク質 / 1次元拡散係数 / p53 / タンパク質溶媒間相互作用 / 誘電緩和分光 / ラマン分光 / 水和自由エネルギー / がん抑制タンパク質 / hyper-mobile water / diffusion constant / protein-DNA affinity / intermolecular force
Outline of Research at the Start

がん抑制機能をもつp53蛋白質は、2重らせんDNA(dsDNA)上を拡散運動し標的配列と強く結合する。本研究ではDNA結合蛋白質とDNAとの結合と探索メカニズム解明に向けて、dsDNAの周りのHMW層の量をbuffer種等で制御したときのp53とdsDNA結合定数測定への影響を実験と計算で調べ、さらに1分子測定によるdsDNA上のp53の1次元拡散係数に及ぼすハイパーモバイル水(HMW)の効果について明らかにする。

Outline of Final Research Achievements

The binding between a protein molecule and DNA is an intermolecular interaction in water. Electrostatic force and van der Waals force are the protagonists and depend on the nature of water. Here, we investigated how the water around DNA differs from the properties of pure water. High-resolution microwave dielectric spectroscopy, high-resolution Raman OH stretch band spectroscopy, and molecular dynamics (MD) computation were used in the study. Dielectric spectroscopy detected water around dsDNA that had a faster and slower orientation response than pure water. And from Raman spectroscopy, a new band of cooperative vibration mode of many water molecules at the low wavenumber side of the OH stretch band of pure water was detected. By these results and MD calculation, it was found that more than ten times the volume of water as DNA is different from pure water. It will deepen our understanding of DNA protein binding and sequence recognition.

Academic Significance and Societal Importance of the Research Achievements

この研究は、dsDNA鎖上をガン抑制蛋白質p53の1次元拡散係数が溶液内のMgやCaイオンの添加により高まるとの論文に興味を持ち、DNA鎖が周りの水に与える影響とDNA周りの水への各イオンの影響を調べるこの研究を進めた。その結果これまで観測されたことのないDNA鎖周りの水の密度等性質が通常水と大きく異なることを高分解誘電とラマン分光法とMD計算で明らかにした。水の性質のDNA-蛋白質等分子間相互作用への影響は物理化学分野の課題であり、DNA関連生化学や医学薬学分野につながると思われる。

Report

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

    (10 results)

All 2021 2020 2019

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] The disordered DNA-binding domain of p53 is indispensable for forming an encounter complex to and jumping along DNA2021

    • Author(s)
      Sbekti D.R.G., Kamagata K.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 534 Pages: 21-26

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transient binding and jumping dynamics of p53 along DNA revealed by sub-millisecond resolved single-molecule fluorescence tracking2020

    • Author(s)
      Subekti D. R. G., Murata A., Itoh Y., Takahashi S., Kamagata K.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 13697-13697

    • DOI

      10.1038/s41598-020-70763-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DNA結合タンパク質研究の最前線2020

    • Author(s)
      鎌形清人
    • Journal Title

      Precision Medicine

      Volume: 3 Pages: 547-553

    • Related Report
      2020 Research-status Report
  • [Journal Article] How p53 molecules solve the target DNA search problem2020

    • Author(s)
      Kamagata, K., Itoh, Y., Subekti, D.R.G.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 3 Pages: 1-13

    • DOI

      10.3390/ijms21031031

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Collective water behavior around charged filaments (DNA) by microwave dielectric relaxation and Raman OH-stretching/bending bands spectroscopy2021

    • Author(s)
      Makoto Suzuki
    • Organizer
      Biophysical Society of Japan Annual Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ラマンOH伸縮バンドの高分解観測によるDNA周りの水の動きやすさ -Mg/Ca イオンの効果-2021

    • Author(s)
      鈴木 誠, 鎌形清人, 高橋 聡, 魚住信之
    • Organizer
      日本生物物理学会北海道・東北支部合同例会
    • Related Report
      2020 Research-status Report
  • [Presentation] アクトミオシンATP分解ステップの 熱力学量を考慮した新たな 駆動モデル2020

    • Author(s)
      鈴木 誠, 最上譲二, 松林伸幸
    • Organizer
      生体運動研究合同班会議(京都)
    • Related Report
      2019 Research-status Report
  • [Presentation] On the physicochemical origin of the driving force of actomyosin motor2019

    • Author(s)
      Makoto Suzuki
    • Organizer
      10th Toyota Riken International Workshop
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] アクトミオシンの力発生機構 -水和測定と高電場下の水和自由エネルギーから-2019

    • Author(s)
      鈴木 誠, 最上譲二, 松林伸幸
    • Organizer
      溶液化学シンポジウム(仙台)
    • Related Report
      2019 Research-status Report
  • [Presentation] アクトミオシンの力発生と蛋白質水和自由エネルギーの電場摂動2019

    • Author(s)
      鈴木 誠, 最上譲二, 松林伸幸
    • Organizer
      筋生理の集い(東京慈恵会医科大学)
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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