Osawa, Masanori



Faculty of Pharmacy, Department of Pharmaceutical Sciences Division of Physics for Life Functions (Shiba-Kyoritsu)




Research Areas 【 Display / hide

  • Structural biochemistry

  • Biophysics

Research Keywords 【 Display / hide

  • ion channel

  • Signal transduction

  • nuclear magnetic resonance

  • structural biology

  • translation factor

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Books 【 Display / hide

  • 【試料分析講座】「蛋白質の分析」

    OSAWA MASANORI, 分析化学会(丸善), 2012

    Scope: NMR・CDスペクトル

  • 分子細胞生物学辞典 (第2版)

    OSAWA MASANORI, 東京化学同人, 2008

    Scope: 「等温滴定型カロリメトリー」,「滴定曲線」

  • 実験医学別冊「生命科学のための機器分析実験ハンドブック」

    OSAWA MASANORI, 羊土社, 2007

    Scope: 「等温滴定型カロリメトリー(ITC) ~熱量測定による相互作用の定量的解析~」

  • 「物理系薬学」 III. 生体分子・化学物質の構造決定

    OSAWA MASANORI, 東京化学同人, 2005

    Scope: 「SBO15 タンパク質の自由度について概説できる」

  • ゲノム創薬・創薬のパラダイムシフト


    Scope: 構造生物学に基づく創薬分子デザイン

Papers 【 Display / hide

  • Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel

    Hanaho Kano, Yuki Toyama, Shunsuke Imai, Yuta Iwahashi, Yoko Mase, Mariko Yokogawa, Masanori Osawa, and Ichio Shimada

    Nat Commun. (Nature Communications)  10 ( 1 )  2019.04

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © 2019, The Author(s). G protein-gated inwardly rectifying potassium channel (GIRK) plays a key role in regulating neurotransmission. GIRK is opened by the direct binding of the G protein βγ subunit (Gβγ), which is released from the heterotrimeric G protein (Gαβγ) upon the activation of G protein-coupled receptors (GPCRs). GIRK contributes to precise cellular responses by specifically and efficiently responding to the Gi/o-coupled GPCRs. However, the detailed mechanisms underlying this family-specific and efficient activation are largely unknown. Here, we investigate the structural mechanism underlying the Gi/o family-specific activation of GIRK, by combining cell-based BRET experiments and NMR analyses in a reconstituted membrane environment. We show that the interaction formed by the αA helix of Gαi/o mediates the formation of the Gαi/oβγ-GIRK complex, which is responsible for the family-specific activation of GIRK. We also present a model structure of the Gαi/oβγ-GIRK complex, which provides the molecular basis underlying the specific and efficient regulation of GIRK.

  • Nanodiscs for Structural Biology in a Membranous Environment

    Mariko Yokogawa, Masahiro Fukuda, Masanori Osawa

    Chem. Pharm. Bull. (Chemical and Pharmaceutical Bulletin)  67 ( 67 ) 321 - 326 2018.11

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00092363

     View Summary

    © 2019 The Pharmaceutical Society of Japan The structures of many membrane proteins have been analyzed in detergent micelles. However, the environment of detergent micelles differs somewhat from that of the lipid bilayer, where membrane proteins exhibit physiological functions. Therefore, a more membrane-like environment has been awaited for structural analysis of membrane proteins. Nanodiscs are “hockey-puck”-shaped lipid bilayer particles that distribute in a monodispersed manner in aqueous solution. We review how nanodiscs or protein-reconstituted nanodiscs are prepared and how they are utilized to analyze protein structure, dynamics, and interactions with lipid molecules using solution NMR and cryo-electron microscopy.

  • Functional roles of Mg <sup>2+</sup> binding sites in ion-dependent gating of a Mg <sup>2+</sup> channel, MgtE, revealed by solution NMR

    Maruyama T., Imai S., Kusakizako T., Hattori M., Ishitani R., Nureki O., Ito K., Maturana A., Shimada I., Osawa M.

    eLife (eLife)  7 2018.04

     View Summary

    © Maruyama et al. Magnesium ions (Mg 2+ ) are divalent cations essential for various cellular functions. Mg 2+ homeostasis is maintained through Mg 2+ channels such as MgtE, a prokaryotic Mg 2+ channel whose gating is regulated by intracellular Mg 2+ levels. Our previous crystal structure of MgtE in the Mg 2+ -bound, closed state revealed the existence of seven crystallographically-independent Mg 2+ -binding sites, Mg1–Mg7. The role of Mg 2+ -binding to each site in channel closure remains unknown. Here, we investigated Mg 2+ -dependent changes in the structure and dynamics of MgtE using nuclear magnetic resonance spectroscopy. Mg 2+ -titration experiments, using wild-type and mutant forms of MgtE, revealed that the Mg 2+ binding sites Mg1, Mg2, Mg3, and Mg6, exhibited cooperativity and a higher affinity for Mg 2+ , enabling the remaining Mg 2+ binding sites, Mg4, Mg5, and Mg7, to play important roles in channel closure. This study revealed the role of each Mg 2+ -binding site in MgtE gating, underlying the mechanism of cellular Mg 2+ homeostasis.

  • Structural basis for the ethanol action on G-protein–activated inwardly rectifying potassium channel 1 revealed by NMR spectroscopy

    Yuki Toyama, Hanaho Kano, Yoko Mase, Mariko Yokogawa, Masanori Osawa and Ichio Shimada

    PNAS  2018.03

    Research paper (scientific journal), Joint Work, Accepted

  • Characterization of the multimeric structure of poly(A)-binding protein on a poly(A) tail

    Sawazaki R., Imai S., Yokogawa M., Hosoda N., Hoshino S., Mio M., Mio K., Shimada I., Osawa M.

    Scientific Reports (Scientific Reports)  8 ( 1 )  2018.01

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    © 2018 The Author(s). Eukaryotic mature mRNAs possess a poly adenylate tail (poly(A)), to which multiple molecules of poly(A)-binding protein C1 (PABPC1) bind. PABPC1 regulates translation and mRNA metabolism by binding to regulatory proteins. To understand functional mechanism of the regulatory proteins, it is necessary to reveal how multiple molecules of PABPC1 exist on poly(A). Here, we characterize the structure of the multiple molecules of PABPC1 on poly(A), by using transmission electron microscopy (TEM), chemical cross-linking, and NMR spectroscopy. The TEM images and chemical cross-linking results indicate that multiple PABPC1 molecules form a wormlike structure in the PABPC1-poly(A) complex, in which the PABPC1 molecules are linearly arrayed. NMR and cross-linking analyses indicate that PABPC1 forms a multimer by binding to the neighbouring PABPC1 molecules via interactions between the RNA recognition motif (RRM) 2 in one molecule and the middle portion of the linker region of another molecule. A PABPC1 mutant lacking the interaction site in the linker, which possesses an impaired ability to form the multimer, reduced the in vitro translation activity, suggesting the importance of PABPC1 multimer formation in the translation process. We therefore propose a model of the PABPC1 multimer that provides clues to comprehensively understand the regulation mechanism of mRNA translation.

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Presentations 【 Display / hide

  • 生物活性情報を利用したコアライブラリー構築法の開発

    清水祐吾 、大澤匡範 、池田和由

    第47回構造活性相関シンポジウム, 2019.12, Poster (general)

  • Elucidation of the inhibitory mechanism of a sea anemone toxin, APETx1, targeting a human heart voltage-gated potassium channel, hERG1.

    松村 一輝、福田昌弘 、簗瀬 尚美 、秋元 まどか 、黒川 洵子 、横川真梨子、大澤 匡範

    第42回 日本分子生物学会, 2019.12, Poster (general)

  • Development of data curation and integration protocol for chemical library in early drug discovery

    Yugo Shimizu, Masanori Osawa,Kazuyoshi Ikeda

    CBI学会2019年大会, 2019.10, Oral Presentation(general)

  • 電位依存性H+ チャネルHv1のアラキドン酸による活性化促進機構の解明

    村上玲 他

    第63回 日本薬学会関東支部大会, 2019.09, Poster (general)

  • リン酸化による転写因子FOXO3a の機能抑制機構の解明


    第63回 日本薬学会関東支部大会, 2019.09, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 14-3-3タンパク質によるリン酸化シグナル経路の熱力学的・構造生物学的基盤


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 大澤 匡範, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 電位センサーを標的とした電位依存性イオンチャネルの機能制御と創薬戦略の構築


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 大澤 匡範, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • リポクオリティと膜蛋白質の相互作用のNMR解析法の開発


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 大澤 匡範, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

Awards 【 Display / hide

  • Best Poster Award

    Masanori Osawa, 2016.07, The organizing committee of International and Interdisciplinary Symposium 2016, Structural Basis for the Inhibition of Voltage-dependent K+ Channel by Gating Modifier Toxin

    Type of Award: Other Awards

  • 長瀬研究振興賞

    2016.04, NAGASE Science Technology Foundation, Development of novel nanodisc that enables solution NMR analyses of membrane protein interactions in the lipid bilayer

    Type of Award: Other Awards


Courses Taught 【 Display / hide











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Courses Previously Taught 【 Display / hide

  • Analytical Chemistry

    Keio University, 2018, Spring Semester, Major subject, Lecture, Within own faculty, 1h, 240people

  • 物理分析学

    Keio University, 2018, Autumn Semester, Major subject, Lecture, 220people

  • Basic pharmaceutical sciences laboratory course

    Keio University, 2018, Autumn Semester, Major subject, Laboratory work/practical work/exercise, 240people

  • Physical chemistry (3)B

    Keio University, 2015, Autumn Semester, Major subject, Lecture, 240people

  • Basic pharmaceutical sciences laboratory course

    Keio University, 2015, Autumn Semester, Major subject, Laboratory work/practical work/exercise, 240people

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