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Unified understanding of the coupled folding and binding mechanisms of intrinsically disordered proteins

Research Project

Project/Area Number 15K07023
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biophysics
Research InstitutionThe University of Tokyo

Principal Investigator

Arai Munehito  東京大学, 大学院総合文化研究科, 教授 (90302801)

Co-Investigator(Renkei-kenkyūsha) HAYASHI Yuuki  東京大学, 大学院総合文化研究科, 助教 (90444059)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords蛋白質 / フォールディング / 天然変性蛋白質 / 分子認識 / NMR
Outline of Final Research Achievements

Intrinsically disordered proteins (IDPs) have disordered structures under physiological conditions but fold into specific structures upon binding to their target proteins. Because many eukaryotic proteins are IDPs, it is important to elucidate the determinants of the mechanisms of coupled folding and binding of IDPs and to unify the understanding of how IDPs recognize their target molecules. Here, we showed that even a single IDP can contain two regions that bind their targets via different binding mechanisms, including the induced-fit and conformational selection mechanisms. Moreover, our results suggest that the folding ability of IDPs determines their binding mechanisms.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (46 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (36 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Remarks (2 results)

  • [Int'l Joint Research] The Scripps Research Institute(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] The Scripps Research Institute(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Unified understanding of folding and binding mechanisms of globular and intrinsically disordered proteins2018

    • Author(s)
      M. Arai
    • Journal Title

      Biophysical Reviews

      Volume: 10 Issue: 2 Pages: 163-181

    • DOI

      10.1007/s12551-017-0346-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Formation of the chaperonin complex studied by 2D NMR spectroscopy2017

    • Author(s)
      Takenaka Toshio、Nakamura Takashi、Yanaka Saeko、Yagi-Utsumi Maho、Chandak Mahesh S.、Takahashi Kazunobu、Paul Subhankar、Makabe Koki、Arai Munehito、Kato Koichi、Kuwajima Kunihiro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 10 Pages: 187022-187022

    • DOI

      10.1371/journal.pone.0187022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Highly Heterogeneous Nature of the Native and Unfolded States of the B Domain of Protein A Revealed by Two-Dimensional Fluorescence Lifetime Correlation Spectroscopy2017

    • Author(s)
      Otosu Takuhiro、Ishii Kunihiko、Oikawa Hiroyuki、Arai Munehito、Takahashi Satoshi、Tahara Tahei
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 121 Issue: 22 Pages: 5463-5473

    • DOI

      10.1021/acs.jpcb.7b00546

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mapping the interactions of adenoviral E1A proteins with the p160 nuclear receptor coactivator binding domain of CBP.2016

    • Author(s)
      Haberz, P., Arai, M., Martinez-Yamout, M.A., Dyson, H.J., & Wright, P.E.
    • Journal Title

      Protein Science

      Volume: 25 Issue: 12 Pages: 2256-2267

    • DOI

      10.1002/pro.3059

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Conformational propensities of intrinsically disordered proteins influence the mechanism of binding and folding2015

    • Author(s)
      Munehito Arai, Kenji Sugase, H, Jane Dyson, Peter E. Wright
    • Journal Title

      Proc. Natl. Acad. Sci. U S A

      Volume: 112 Issue: 31 Pages: 9614-9619

    • DOI

      10.1073/pnas.1512799112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Complexity of the folding transition of the B domain of protein A revealed by the high-speed tracking of single-molecule fluorescence time series2015

    • Author(s)
      Hiroyuki Oikawa, Kiyoto Kamagata, Munehito Arai, Satoshi Takahashi
    • Journal Title

      J. Phys. Chem. B

      Volume: 119 Issue: 20 Pages: 6081-6091

    • DOI

      10.1021/acs.jpcb.5b00414

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 天然変性タンパク質HIV-1 Tatの構造特性と分子認識2018

    • Author(s)
      椢原朋子、林勇樹、工藤恒、河合秀信、岡芳樹、新井宗仁
    • Organizer
      第7回日本生物物理学会関東支部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞内GTP定量センサーの開発2018

    • Author(s)
      岡芳樹、竹内恒、林勇樹、新井宗仁
    • Organizer
      第7回日本生物物理学会関東支部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 天然変性タンパク質を利用した創薬基盤技術の開発2017

    • Author(s)
      新井宗仁
    • Organizer
      第6回岐阜構造生物学・医学・論理的創薬研究会シンポジウム
    • Place of Presentation
      岐阜大学(岐阜県岐阜市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 合理的設計による抗体精製用アフィニティーリガンドFPAの改良2017

    • Author(s)
      岡芳樹、澤田泰平、渡辺尚大、工藤恒、和田愛未、河合秀信、張マリ、林勇樹、新井宗仁
    • Organizer
      第6回日本生物物理学会関東支部会
    • Place of Presentation
      早稲田大学先端生命医科学センター(東京都新宿区)
    • Year and Date
      2017-03-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 中性に近いpHで抗体を精製可能な新規アフィニティーカラムの開発2017

    • Author(s)
      岡芳樹、澤田泰平、渡辺尚大、工藤恒、和田愛未、河合秀信、張マリ、林勇樹、新井宗仁
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 天然変性タンパク質による標的分子認識機構2017

    • Author(s)
      新井宗仁
    • Organizer
      第18回若手NMR研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 天然変性蛋白質による標的分子認識機構の解明2017

    • Author(s)
      新井宗仁
    • Organizer
      2017旭硝子財団 助成研究発表会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] c-Myb-KIX 間相互作用を阻害するペプチドの合理的設計2017

    • Author(s)
      季高駿士、岡芳樹 、林勇樹 、新井宗仁
    • Organizer
      第17回日本蛋白質科学会年会ワークショップ「タンパク質科学における理論と実験の協奏」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 天然変性タンパク質c-Jun と転写コアクチベータCBP のKIX ドメインの相互作用2017

    • Author(s)
      吉崎慧、末松佑麿、季高駿士、椢原朋子、林勇樹、新井宗仁
    • Organizer
      第17回日本蛋白質科学会年会ワークショップ「天然変性領域及びマルチサブユニット複合体の機能解析」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 天然変性タンパク質HIV-1 Tatの亜鉛とpHに依存した構造多様性2017

    • Author(s)
      椢原朋子、林勇樹、工藤恒、河合秀信、岡芳樹、新井宗仁
    • Organizer
      第17回日本蛋白質科学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 合理的設計による新規抗体精製用アフィニティーリガンドの開発2017

    • Author(s)
      岡芳樹、澤田泰平、渡辺尚大、工藤恒、和田愛未、河合秀信、張マリ、林勇樹、新井宗仁
    • Organizer
      第17回日本蛋白質科学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Statistical analysis on the molecular size of native proteins2016

    • Author(s)
      河合秀信、高橋大輔、新井宗仁
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Rational design of a peptide inhibitor of the c-Myb-KIX interaction2016

    • Author(s)
      Shunji Suetaka, Yoshiki Oka, Yuuki Hayashi, Munehito Arai
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Statistical analysis on the structural properties of native proteins2016

    • Author(s)
      Hidenobu Kawai, Daisuke Takahashi, Munehito Arai
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Rational design of FPA, a ligand for antibody purification2016

    • Author(s)
      Yoshiki Oka, Taihei Sawada1, Takahiro Watanabe, Hisashi Kudo, Manami Wada, Hidenobu Kawai, Mari Chang, Yuuki Hayashi, Munehito Arai
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Conformational diversity in the intrinsically disordered HIV-1 Tat protein induced by zinc and pH2016

    • Author(s)
      Tomoko Kunihara, Yuuki Hayashi, Hisashi Kudo, Hidenobu Kawai, Yoshiki Oka, Munehito Arai
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Interaction of the intrinsically disordered c-Jun with the KIX domain of the transcriptional coactivator CBP2016

    • Author(s)
      Satoru Yoshizaki, Tomoko Kunihara, Yuuki Hayashi, and Munehito Arai
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Conformational propensities of intrinsically disordered proteins influence the mechanism of binding and folding2016

    • Author(s)
      Munehito Arai, Kenji Sugase, H. Jane Dyson, Peter E. Wright
    • Organizer
      ICMRBS2016 (27th 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
      2016-08-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural analysis of the intrinsically disordered HIV-1 Tat protein2016

    • Author(s)
      Tomoko Kunihara, Yuuki Hayashi, Hisashi Kudo, Hidenobu Kawai, Yoshiki Oka, Munehito Arai
    • Organizer
      ICMRBS2016 (27th 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
      2016-08-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 合理的設計による抗体精製用リガンドFPAの開発2016

    • Author(s)
      岡芳樹、澤田泰平、渡辺尚大、林勇樹、新井宗仁
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-06-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 天然変性タンパク質HIV-1 Tatの立体構造解析2016

    • Author(s)
      椢原朋子、林勇樹、工藤恒、河合秀信、岡芳樹、新井宗仁
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-06-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 天然タンパク質の立体構造物性に関する統計解析2016

    • Author(s)
      河合秀信、高橋大輔、新井宗仁
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-06-08
    • Related Report
      2016 Research-status Report
  • [Presentation] タンパク質のフォールディングとデザイン2016

    • Author(s)
      新井宗仁
    • Organizer
      東京大学 大学院理学系研究科 物理学専攻 A7サブコース 第3回シンポジウム「生物物理の新展開」
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 天然変性タンパク質HIV-1 Tatの立体構造解析2016

    • Author(s)
      椢原朋子、林勇樹、工藤恒、河合秀信、岡芳樹、新井宗仁
    • Organizer
      第16回 東京大学生命科学シンポジウム
    • Place of Presentation
      東京大学(東京都目黒区)
    • Year and Date
      2016-04-23
    • Related Report
      2016 Research-status Report
  • [Presentation] 合理的設計による抗体精製用リガンドFPAの開発2016

    • Author(s)
      岡芳樹、澤田泰平、渡辺尚大、林勇樹、新井宗仁
    • Organizer
      第5回日本生物物理学会関東支部会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県桐生市)
    • Year and Date
      2016-03-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 天然変性タンパク質HIV-1 Tatの立体構造解析2016

    • Author(s)
      椢原朋子、林勇樹、工藤恒、河合秀信、岡芳樹、新井宗仁
    • Organizer
      第5回日本生物物理学会関東支部会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県桐生市)
    • Year and Date
      2016-03-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 天然タンパク質の立体構造物性に関する統計解析2016

    • Author(s)
      河合秀信、高橋大輔、新井宗仁
    • Organizer
      第5回日本生物物理学会関東支部会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県桐生市)
    • Year and Date
      2016-03-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Complex folding transition of the B domain of protein A investigated by the high-speed measurement of single-molecule FRET time series2015

    • Author(s)
      Hiroyuki Oikawa, Kiyoto Kamagata, Munehito Arai, Satoshi Takahashi
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] pH-dependent conformational changes in the intrinsically disordered HIV-1 Tat protein2015

    • Author(s)
      Tomoko Kunihara, Yuuki Hayashi, Munehito Arai
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Tracking microsecond single-molecule FRET dynamics on the fast protein folding by the line-confocal microscopy2015

    • Author(s)
      Hiroyuki Oikawa, Munehito Arai, Atsuhito Fukasawa, Hiroaki Yokota, Toru Ide, Satoshi Takahashi
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Relaxation and lineshape analysis for electron paramagnetic resonance of doubly spin-labeled protein with structural distribution2015

    • Author(s)
      Yasunori Ohba, Munehito Arai, Jun Abe, Tetsuya Itabashi, Toshikazu Nakamura, Satoshi Takahashi, Seigo Yamauchi
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Statistical analysis on the molecular density of native proteins2015

    • Author(s)
      Hidenobu Kawai, Munehito Arai
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Herstatin, an antitumor drug candidate, is an intrinsically disordered protein2015

    • Author(s)
      Daisuke Tashiro, Yuuki Hayashi, Munehito Arai
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Rational design to improve the pH-sensitive antibody dissociation of FPA, a ligand for antibody purification2015

    • Author(s)
      Taihei Sawada, Yoshiki Oka, Takahiro Watanabe, Yuuki Hayashi, Munehito Arai
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Presentation] 天然変性タンパク質HIV-1 Tatと転写コアクチベーターCBPのKIXドメインとの相互作用2015

    • Author(s)
      椢原朋子、林勇樹、新井宗仁
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 天然タンパク質の分子サイズ特性に関する統計解析2015

    • Author(s)
      河合秀信、高橋大輔、新井宗仁
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
  • [Remarks] 新井研究室のホームページ

    • URL

      http://folding.c.u-tokyo.ac.jp

    • Related Report
      2017 Annual Research Report
  • [Remarks] 新井研究室のホームページ

    • URL

      http://folding.c.u-tokyo.ac.jp/

    • Related Report
      2016 Research-status Report 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2022-02-16  

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