Piezoelectric effect in proteins: a novel mechanism of allostery

• Project/Area Number: 16K14715
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biophysics
• Research Institution: Waseda University
• Principal Investigator: Takano Mitsunori 早稲田大学, 理工学術院, 教授 (40313168)
• Research Collaborator: Sato Takato ; Ohnuki Jun
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: アロステリー / 分子機械 / 圧電応答 / 誘電応答 / アロステリック機構 / タンパク質 / 圧電効果

Outline of Final Research Achievements

The vital activities of living organisms are ultimately based on the functions of protein molecules and the highly-organized intermolecular interaction network among the proteins and other biomolecules. The motility, for example, is based on the association and dissociation dynamics of actin and myosin molecules that is regulated by ATP (energy-supplying biomolecule). In this study, by using high-performance computers, we elucidated the input-output characteristics (particularly piezoelectric and dielectric responses) of the molecular device of protein to advance the physical understanding of how a single protein molecule works and how the intermolecular interactions are regulated.

Academic Significance and Societal Importance of the Research Achievements

もしミオシンの正常に機能しなくなったり、あるいはATPによるミオシンとアクチンの結合と解離の制御がうまくいかなくなることあれば、私たちの運動機能（たとえば心臓の収縮弛緩運動）は大きなダメージを受ける。タンパク質1分子がどのように機能するか、分子間相互作用がどのように制御されるかの物理基盤が明らかになればタンパク質分子物性の基礎科学として学術的意義が大きいのみならず、それらが正常に機能しなくなったときの根本的な原因究明（原因療法）につながる可能性がある。

Research Products

• [Journal Article] Hydrophobic Surface Enhances Electrostatic Interaction in Water (2018)
  • Author(s): Sato Takato、Sasaki Tohru、Ohnuki Jun、Umezawa Koji、Takano Mitsunori
  • Journal Title: Physical Review Letters Volume: 121 Issue: 20 Pages: 206002-206002
  • DOI: 10.1103/physrevlett.121.206002
  • Peer Reviewed
• [Journal Article] Orchestrated Electrostatic Interactions Among Myosin, Actin, ATP, and Water (2018)
  • Author(s): Takano Mitsunori
  • Journal Title: The Role of Water in ATP Hydrolysis Energy Transduction by Protein Machinery Volume: - Pages: 113-122
  • DOI: 10.1007/978-981-10-8459-1_8
  • ISBN: 9789811084584, 9789811084591
• [Journal Article] Structural and dynamical characteristics of tropomyosin epitopes as the major allergens in shrimp (2018)
  • Author(s): Ozawa Hideo、Umezawa Koji、Takano Mitsunori、Ishizaki Shoichiro、Watabe Shugo、Ochiai Yoshihiro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 498 Issue: 1 Pages: 119-124
  • DOI: 10.1016/j.bbrc.2018.02.172
  • Peer Reviewed
• [Journal Article] Long-range coupling between ATP-binding and lever-arm regions in myosin via dielectric allostery (2017)
  • Author(s): Sato Takato、Ohnuki Jun、Takano Mitsunori
  • Journal Title: The Journal of Chemical Physics Volume: 147 Issue: 21 Pages: 215101-215101
  • DOI: 10.1063/1.5004809
  • Peer Reviewed
• [Journal Article] Electrostatic balance between global repulsion and local attraction in reentrant polymerization of actin (2017)
  • Author(s): Ohnuki Jun、Yodogawa Akira、Takano Mitsunori
  • Journal Title: Cytoskeleton Volume: 74 Issue: 12 Pages: 504-511
  • DOI: 10.1002/cm.21391
  • Peer Reviewed
• [Journal Article] Over-destabilization of protein-protein interaction in Generalized Born model and utility of energy density integration cutoff (2017)
  • Author(s): Y. Mizuhara, D. Parkin, K. Umezawa, J. Ohnuki, M. Takano
  • Journal Title: J. Phys. Chem. B Volume: 121 Issue: 18 Pages: 4669-4677
  • DOI: 10.1021/acs.jpcb.7b01438
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Piezoelectric allostery of protein (2016)
  • Author(s): J. Ohnuki, T. Sato, M. Takano
  • Journal Title: Phys. Rev. E Volume: 94 Issue: 1 Pages: 012406-012406
  • DOI: 10.1103/physreve.94.012406
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dielectric allostery of protein: Response of myosin to ATP binding (2016)
  • Author(s): T. Sato, J. Ohnuki, M. Takano
  • Journal Title: J. Phys. Chem. B Volume: 120 Issue: 51 Pages: 13047-13055
  • DOI: 10.1021/acs.jpcb.6b10003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intrinsic disorder accelerates dissociation rather than association (2016)
  • Author(s): K. Umezawa, J. Ohnuki, J. Higo, and M. Takano
  • Journal Title: Proteins: Structure, Function and Bioinformatics Volume: - Issue: 8 Pages: 1489-1501
  • DOI: 10.1002/prot.25057
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Depolymerization mechanism of actin due to dielectric allostery (2019)
  • Author(s): Jun Ohnuki, Mitsunori Takano
  • Organizer: Biophysical Society 63rd Annual Meeting
  • Int'l Joint Research
• [Presentation] 誘電アロステリ―によるアクチンを基盤とした生体運動の物理機構 (2019)
  • Author(s): 大貫隼、高野光則
  • Organizer: 生体運動研究合同班会議
• [Presentation] Coulombic interaction network and novel allostery in molecular machines (2018)
  • Author(s): Mitsunori Takano
  • Organizer: 56th Annual Meeting of Biophysical Society of Japan
  • Int'l Joint Research / Invited
• [Presentation] Piezoelectric and dielectric allostery of an actin filament and its effect on binding preference of cofilin (2018)
  • Author(s): Jun Ohnuki, Akira Yodogawa, Takato Sato, Mitsunori Takano
  • Organizer: 56th Annual Meeting of Biophysical Society of Japan
  • Int'l Joint Research
• [Presentation] Coupling of the Redox and Structural States in Cytochrome P450 Reductase Studied by Molecular Dynamics Simulation (2018)
  • Author(s): Mikuru Iijima, Jun Ohnuki, Takato Sato, Masakazu Sugishima, Mitsunori Takano
  • Organizer: The Protein Society 32nd Annual Symposium
  • Int'l Joint Research
• [Presentation] 分子機械の圧電アロステリ―：アクチンフィラメントのメカノセンシングの物理機構 (2018)
  • Author(s): 大貫隼、高野光則
  • Organizer: 生体運動研究合同班会議
• [Presentation] 分子機械の誘電アロステリ―：ATP結合によるリバースジャイレースの超らせん導入の物理機構 (2018)
  • Author(s): 森竹亮太、佐藤昂人、高野光則
  • Organizer: 生体運動研究合同班会議
• [Presentation] アクチンの荷電状態とサブユニット間静電相互作用のpH依存性 (2018)
  • Author(s): 山下昴、大貫隼、高野光則
  • Organizer: 第7回日本生物物理学会関東支部会
• [Presentation] アクチンフィラメントの圧電アロステリ― (2017)
  • Author(s): 大貫隼、高野光則
  • Organizer: 第７回分子モーター討論会
  • Invited
• [Presentation] Mechano-electrical communications in actin filament (2017)
  • Author(s): 大貫隼、高野光則
  • Organizer: 日本生物物理学会第55回年会
  • Invited
• [Presentation] Tension-induced electrostatic change in actin: piezoelectricity of an actin filament (2017)
  • Author(s): 大貫隼、淀川良、佐藤昂人、上田太郎、高野光則
  • Organizer: 日本生物物理学会第55回年会
• [Presentation] Counter-ion-induced electrostatic change in actin: the balance between global repulsion and local attraction in reentrant polymerization (2017)
  • Author(s): 淀川良、大貫隼、高野光則
  • Organizer: 日本生物物理学会第55回年会
• [Presentation] 誘電アロステリ―による分子モーターの力発生機構 (2017)
  • Author(s): 佐藤昂人、大貫隼、高野光則
  • Organizer: 第31回分子シミュレーション討論会
• [Presentation] シトクロムP450還元酵素の誘電応答が制御する大規模構造変化と電子伝達 (2017)
  • Author(s): 飯島美来、佐藤昂人、森竹亮太、高野光則
  • Organizer: 第31回分子シミュレーション討論会
• [Presentation] Piezoelectric Allostery of an Actin Filament (2016)
  • Author(s): J. Ohnuki, T. Sato, H. Okamura, T.Q.P. Uyeda, M. Takano
  • Organizer: IGER International Symposium on "Now in actin"
  • Place of Presentation: 名古屋
  • Year and Date: 2016-12-11
  • Int'l Joint Research
• [Presentation] Piezoelectric Allostery of Protein (2016)
  • Author(s): J. Ohnuki, T. Sato, M. Takano
  • Organizer: Protein Electrostatics Berlin 2016
  • Place of Presentation: Berlin
  • Int'l Joint Research
• [Presentation] Critical Role of Cutoff Parameter to Calculate Effective Born Radii in Simulating Protein-Protein Interaction (2016)
  • Author(s): Y. Mizuhara, D. Parkin, M. Takano
  • Organizer: Protein Electrostatics Berlin 2016
  • Place of Presentation: Berlin
  • Int'l Joint Research
• [Presentation] Piezoelectric property of an actin filament III (2016)
  • Author(s): 大貫隼、佐藤昂人、岡村英世、上田太郎、高野光則
  • Organizer: 日本生物物理学会第54回年会
  • Place of Presentation: つくば
  • Int'l Joint Research
• [Book] The Role of Water in ATP Hydrolysis Energy Transduction by Protein Machinery (M. Suzuki Ed.) (2018)
  • Author(s): Mitsunori Takano
  • Total Pages: 10
  • Publisher: Springer
• [Book] 分子マシンの科学 (2017)
  • Author(s): 日本化学会編
  • Total Pages: 200
  • Publisher: 化学同人
  • ISBN: 9784759813869