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Analysis of functional dynamics of membrane proteins in different membrane environments

Research Project

Project/Area Number 18H02393
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionYokohama City University

Principal Investigator

Takahashi Hideo  横浜市立大学, 生命医科学研究科, 教授 (60265717)

Co-Investigator(Kenkyū-buntansha) 竹内 恒  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (20581284)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
KeywordsNMR / 膜タンパク質 / 界面活性剤 / 脂質 / 酵素
Outline of Final Research Achievements

In this study, we showed that the enzymatic activity of a rhomboid protease is regulated by the alkyl chain length and the properties of hydrophilic head groups of solubilized detergents. And it was found that the enzymatic activity is inversely correlated with the thermal stability of the molecule, which inferred that the internal dynamics of the rhomboid protease affects the enzymatic activities. Using microbial rhodopsin derived from thermophilic eubacteria, we performed a systematic analysis of the thermal stability in different membrane mimetics including bicelles and nanodiscs, which provides us a useful index of choices of membrane environments for functional and structural analyses of membrane proteins. Furthermore, NMR analysis of the rhodopsin in different environments revealed that the environmental difference induces local structural changes that affect the thermal stability of the molecule.

Academic Significance and Societal Importance of the Research Achievements

膜タンパク質は高い疎水性を有し、水溶液中に単離することが困難であるため、その研究を進めるうえでは界面活性剤などの膜様物質とともに可溶化することが行われる。しかしながら、選択した膜様環境において、構造・機能・安定性がどのように維持されるかという点は、学術的にも、創薬研究や分子工学研究などの応用研究を展開する上でも重要な問題となる。本研究で得られた知見は、他の膜タンパク質研究を進めるうえでの指標となるばかりでなく、周辺環境が膜タンパク質に及ぼす影響を原子レベルで理解するための端緒となる研究成果であるといえる。

Report

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

    (43 results)

All 2022 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 6 results) Presentation (27 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (2 results)

  • [Journal Article] Nonthermal excitation effects mediated by subterahertz radiation on hydrogen exchange in ubiquitin2021

    • Author(s)
      Tokunaga Yuji、Tanaka Masahito、Iida Hitoshi、Kinoshita Moto、Tojima Yuya、Takeuchi Koh、Imashimizu Masahiko
    • Journal Title

      Biophysical Journal

      Volume: 120 Issue: 12 Pages: 1-8

    • DOI

      10.1016/j.bpj.2021.04.013

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Function-Related Dynamics in Multi-Spanning Helical Membrane Proteins Revealed by Solution NMR2021

    • Author(s)
      Takeuchi Koh、Kofuku Yutaka、Imai Shunsuke、Ueda Takumi、Tokunaga Yuji、Toyama Yuki、Shiraishi Yutaro、Shimada Ichio
    • Journal Title

      Membranes

      Volume: 11 Issue: 8 Pages: 604-604

    • DOI

      10.3390/membranes11080604

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flexibility and cell permeability of cyclic Ras-inhibitor peptides revealed by coupled Nose Hoover equation2021

    • Author(s)
      Kei Moritsugu, Koh Takeuchi, Narutoshi Kamiya, Junichi Higo, Isao Yasumatsu, Yoshifumi Fukunishi and Ikuo Fukuda
    • Journal Title

      Journal of Chemical Information and Modeling

      Volume: 61 Issue: 4 Pages: 1921-1930

    • DOI

      10.1021/acs.jcim.0c01427

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery”2020

    • Author(s)
      Hiroyuki Hanzawa, Takashi Shimada, Mizuki Takahashi and Hideo Takahashi
    • Journal Title

      Journal of Biomolecular NMR

      Volume: 74 Issue: 10-11 Pages: 501-508

    • DOI

      10.1007/s10858-020-00314-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural Fingerprints of an Intact Monoclonal Antibody Acquired under Formulated Storage Conditions via 15N Direct Detection Nuclear Magnetic Resonance2020

    • Author(s)
      Tokunaga Yuji、Takeuchi Koh、Okude Junya、Ori Kazutomo、Torizawa Takuya、Shimada Ichio
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: - Issue: 10 Pages: 5360-5366

    • DOI

      10.1021/acs.jmedchem.0c00231

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting the cryptic sites: NMR-based strategy to improve protein druggability by controlling the conformational equilibrium2020

    • Author(s)
      Mizukoshi Yumiko、Takeuchi Koh、Tokunaga Yuji、Matsuo Hitomi、Imai Misaki、Fujisaki Miwa、Kamoshida Hajime、Takizawa Takeshi、Hanzawa Hiroyuki、Shimada Ichio
    • Journal Title

      Science Advances

      Volume: 6 Issue: 40

    • DOI

      10.1126/sciadv.abd0480

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cooperative interactions facilitate stimulation of Rad51 by the Swi5-Sfr1 auxiliary factor complex.2020

    • Author(s)
      Argunhan B, Sakakura M, Afshar N, Kurihara M, Ito K, Maki T, Kanamaru S, Murayama Y, Tsubouchi H, Takahashi M, Takahashi H, Iwasaki H.
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.52566

    • NAID

      120007117502

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural mechanisms underlying activity changes in an AMPA-type glutamate receptor induced by substitutions in its ligand-binding domain2019

    • Author(s)
      Masayoshi Sakakura, Yumi Ohkubo, Hiraku Oshima, Suyong Re, Masahiro Ito, Yuji Sugita, and Hideo Takahashi
    • Journal Title

      Structure

      Volume: 27 Issue: 11 Pages: 1698-1709

    • DOI

      10.1016/j.str.2019.09.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conformational equilibrium defines the variable induction of the multidrug-binding transcriptional repressor QacR2019

    • Author(s)
      Koh Takeuchi, Misaki Imai, and Ichio Shimada
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 116 Issue: 40 Pages: 19963-19972

    • DOI

      10.1073/pnas.1906129116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging solution NMR methods to illuminate the structural and dynamic properties of proteins2019

    • Author(s)
      Haribabu Arthanari, KohTakeuchi, Abhinav Dubey, and Gerhard Wagner
    • Journal Title

      Curr. Opin. Struct. Biol.

      Volume: 58 Pages: 294-304

    • DOI

      10.1016/j.sbi.2019.06.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Population shift mechanism for partial agonism of AMPA receptor2019

    • Author(s)
      Oshima H, Re S, Sakakura M, Takahashi H, Sugita Y.
    • Journal Title

      Biophys. J.

      Volume: 116 Issue: 1 Pages: 52-68

    • DOI

      10.1016/j.bpj.2018.11.3122

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aromatic 19F-13C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics2019

    • Author(s)
      Boeszoermenyi A, Chhabra S, Dubey A, Radeva D. L, Burdzhiev N. T, Chanev C. D, Petrov O. I, Gelev V. M, Zhang M, Anklin C, Kovacs H, Wagner G, Kuprov I, Takeuchi K, Arthanari H.
    • Journal Title

      Nat. Methods

      Volume: 16 Issue: 4 Pages: 333-340

    • DOI

      10.1038/s41592-019-0334-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Phosphoinositide binding by the PH domain in ceramide transfer protein (CERT) is inhibited by hyperphosphorylation of an adjacent serine-repeat motif2018

    • Author(s)
      Sugiki Toshihiko、Egawa Daichi、Kumagai Keigo、Kojima Chojiro、Fujiwara Toshimichi、Takeuchi Koh、Shimada Ichio、Hanada Kentaro、Takahashi Hideo
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 28 Pages: 11206-11217

    • DOI

      10.1074/jbc.ra118.002465

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methyl-selective isotope labeling using α-ketoisovalerate for the yeast Pichia pastoris recombinant protein expression system2018

    • Author(s)
      Suzuki Rika、Sakakura Masayoshi、Mori Masaki、Fujii Moe、Akashi Satoko、Takahashi Hideo
    • Journal Title

      Journal of Biomolecular NMR

      Volume: 71 Issue: 4 Pages: 213-223

    • DOI

      10.1007/s10858-018-0192-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] シャルコー・マリー・トゥース病関連変異型ミエリンタンパク質ゼロの機能構造解析2022

    • Author(s)
      坂倉正義、三尾和弘、田辺幹雄、高橋栄夫
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Solution NMR analysis of Rubrobacter xylanophilus rhodopsin in different membrane-mimetic environments2021

    • Author(s)
      Rika Suzuki, Masafumi Hirohata, Chika Hoyano, Keiichi Kojima, Yuki Sudo, and Hideo Takahashi
    • Organizer
      22nd ICMRBS & 9th APNMR
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体発動分子の機能構造解析に向けた検討2021

    • Author(s)
      鈴木里佳、廣畑雅史、穂谷野知佳、藤田陽、高橋栄夫
    • Organizer
      第1回発動分子科学研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 異なる膜様環境下におけるプロトンポンプ型ロドプシンRxRの機能および構造変化の解析2021

    • Author(s)
      廣畑雅史、鈴木里佳、穂谷野知佳、藤田陽、吉田真帆子、村田武士、小島慧一、須藤雄気、高橋栄夫
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] プロトンポンプ型ロドプシンTRのNMR解析に向けた試料調製法の確立2021

    • Author(s)
      穂谷野知佳、鈴木里佳、廣畑雅史、村田武士、小島慧一、須藤雄気、高橋栄夫
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] シャルコー・マリー・トゥース病関連変異がミエリンタンパク質ゼロの構造および機能に及ぼす影響の解明2021

    • Author(s)
      坂倉正義、三尾和弘、田辺幹雄、高橋栄夫
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 溶液NMR法を用いた光駆動プロトンポンプRxRの機能構造解析2021

    • Author(s)
      鈴木里佳、廣畑雅史、穂谷野知佳、藤田陽、高橋栄夫
    • Organizer
      第2回発動分子科学研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] NMRを用いた動的生命現象の理解と創薬への応用2021

    • Author(s)
      竹内恒
    • Organizer
      第65回日本薬学会関東支部大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 神経栄養因子NGF高親和性受容体TrkAドメイン5と新規結合ペプチドの相互作用解析2021

    • Author(s)
      鈴木里佳、登坂綺水、浴本亨、髙橋真帆、山根努、坂倉正義、水越弓子、竹内恒、嶋田一夫、池口満徳、高橋栄夫
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脂質二重膜の多重層化に重要なミエリンタンパク質ゼロ細胞外ドメインのホモ相互作用メカニズムの解明2021

    • Author(s)
      坂倉正義、田辺幹雄、三尾和弘、高橋栄夫
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 溶液NMRを用いた微生物型プロトンポンプロドプシンRxRの機能・構造解析2020

    • Author(s)
      廣畑雅史、鈴木里佳、小島慧一、吉田真帆子、村田武士、須藤雄気、高橋栄夫
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脂質二重膜の重層化を担うミエリンタンパク質ゼロ細胞外ドメインのホモ相互作用メカニズムの解明2020

    • Author(s)
      坂倉正義、田辺幹雄、三尾和弘、高橋栄夫
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 溶液NMRを用いた動的構造創薬2020

    • Author(s)
      竹内恒
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 溶液NMRを用いた動的構造創薬2020

    • Author(s)
      竹内恒
    • Organizer
      2020年度 日本分光学会NMR分光部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] NMR相互作用解析による創薬アプローチ2019

    • Author(s)
      高橋栄夫
    • Organizer
      生有研シンポジウム「生体分子間に働く相互作用解析法の現状と今後の可能性」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 溶液NMR法を用いた界面活性剤ミセル中における膜タンパク質の比較構造解析2019

    • Author(s)
      里佳、吉田真帆子、廣畑雅史、村田武士、小島慧一、須藤雄気、高橋栄夫
    • Organizer
      第58回NMR討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] リコンビナーゼRad51と補助因子Swi5-Sfr1のNMR相互作用解析に向けた基盤研究2019

    • Author(s)
      井出優希、坂倉正義、真木孝尚、岩崎博史、高橋栄夫
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Rhomboid proteaseの様々な膜環境変化における酵素活性と熱安定性の評価2019

    • Author(s)
      薬袋勇樹、畠山彩由子、平島かれん、坂倉正義、高橋栄夫
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 異なる疑似膜環境中における耐熱性膜タンパク質RxRの構造安定性と機能の解析2019

    • Author(s)
      吉田真帆子、鈴木里佳、廣畑雅史、村田武士、小島慧一、須藤雄気、高橋栄夫
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Conformational equilibrium defines variable transcriptional repression of a multidrug binding transcriptional repressor, QacR2019

    • Author(s)
      Koh Takeuchi
    • Organizer
      8th Asia-Pacific NMR Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Targeting the cryptic sites: NMR-based strategy to improve the draggability of proteins by controlling the conformational equilibrium.2019

    • Author(s)
      Ko Takeuchi
    • Organizer
      第57回生物物理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] NMRを用いたAMPA型グルタミン酸受容体リガンド結合ドメインの運動性解析2018

    • Author(s)
      大久保優美、坂倉正義、横井誠矢、高橋栄夫
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Rhomboid proteaseの活性メカニズム解明に向けた機能・構造解析2018

    • Author(s)
      畠山彩由子、薬袋勇樹、長倉玲音、坂倉正義、高橋栄夫
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 末梢神経ミエリンの膜重層化に関与するタンパク質MPZと脂質との相互作用解析2018

    • Author(s)
      森雅樹、坂倉正義、三尾和弘、高橋栄夫
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] NMR analysis of the structural and functional stability of proteins2018

    • Author(s)
      Hideo Takahashi
    • Organizer
      The 6th International Symposium on Drug Discovery and Design by NMR
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Methyl-selective 13C incorporation using alpha-ketoisovalerate for the yeast Pichia pastoris expression system2018

    • Author(s)
      Rika Suzuki, Masayoshi Sakakura, Hideo Takahashi
    • Organizer
      XXVIII International Conference on Magnetic Resonance in Biological Systems
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NMR を用いたアミロイド前駆蛋白質 C99 の構造解析2018

    • Author(s)
      坂倉正義、真嶋健大、三尾和弘、Charles Sanders、高橋栄夫
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Book] 先端の分析法 第2版 第2章2.多次元NMR測定2022

    • Author(s)
      高橋栄夫
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860437374
    • Related Report
      2021 Annual Research Report
  • [Book] NMRによる有機材料分析とその試料前処理、データ解釈 第6章第5節 NMRによるペプチドの立体構造解析2021

    • Author(s)
      坂倉正義、高橋栄夫
    • Publisher
      技術情報協会
    • ISBN
      9784861048609
    • Related Report
      2021 Annual Research Report

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

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