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Understanding of antigen recognition mechanism of multispecific antibodies

Research Project

Project/Area Number 15K07024
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biophysics
Research InstitutionGifu University

Principal Investigator

KAMATARI Yuji  岐阜大学, 生命科学総合研究支援センター, 助教 (70342772)

Co-Investigator(Kenkyū-buntansha) 織田 昌幸  京都府立大学, 生命環境科学研究科, 准教授 (20318231)
Co-Investigator(Renkei-kenkyūsha) KUWATA Kazuo  岐阜大学, 連合創薬医療情報研究科, 教授 (00170142)
ISHIGURO Naotaka  岐阜大学, 応用生物科学部, 教授 (00109521)
AKASAKA Kazuyuki  近畿大学, 先端技術総合研究所, 教授 (50025368)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsタンパク質 / 抗体 / 抗原認識機構 / 揺らぎ / 準安定状態 / NMR
Outline of Final Research Achievements

In general, a monoclonal antibody (mAb) bind only one antigen (Ag). However, we found an mAb G2 capable of specifically recognizing multiple Ags. The purpose of this study is to understand the Ag recognition mechanism of G2. This study suggested that the Ag-binding site of G2 was flexible in the free form and capable of adapting to at least three different conformations to enable interactions with three different Ags. Further development of this research may lead to extension of the concept of Ag recognition of mAbs, understanding of molecular evolution of proteins, and creation of novel antibody medicine that inhibits two pathways at the same time.

Report

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

    (45 results)

All 2018 2017 2016 2015 Other

All Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Remarks (7 results)

  • [Journal Article] Identification of alprenolol hydrochloride as an anti-prion compound using surface plasmon resonance imaging2018

    • Author(s)
      Y. Miyazaki, T. Ishikawa, Y. O. Kamatari, T. Nakagaki, H. Takatsuki, D. Ishibashi, K. Kuwata, N. Nishida*, R. Atarashi
    • Journal Title

      Mol. Neurobiol

      Volume: 印刷中 Issue: 1 Pages: 367-377

    • DOI

      10.1007/s12035-018-1088-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular basis for diversification of yeast prion strain conformation2018

    • Author(s)
      Ohhashi Yumiko、Yamaguchi Yoshiki、Kurahashi Hiroshi、Kamatari Yuji O.、Sugiyama Shinju、Uluca Boran、Piechatzek Timo、Komi Yusuke、Shida Toshinobu、M?ller Henrik、Hanashima Shinya、Heise Henrike、Kuwata Kazuo、Tanaka Motomasa
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 10 Pages: 2389-2394

    • DOI

      10.1073/pnas.1715483115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A multispecific monoclonal antibody G2 recognizes at least three completely different epitope sequences with high affinity2017

    • Author(s)
      Mahmud MN, Oda M, Usui D, Inoshima Y, Ishiguro N, Kamatari YO.
    • Journal Title

      Protein Sci

      Volume: 26 Issue: 11 Pages: 2162-2169

    • DOI

      10.1002/pro.3263

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Light-chain residue 95 is critical for antigen binding and multispecificity of monoclonal antibody G22017

    • Author(s)
      Usui D, Inaba S, Kamatari YO, Ishiguro N, Oda M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 490 Issue: 4 Pages: 1205-1209

    • DOI

      10.1016/j.bbrc.2017.06.183

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Instability of C154Y variant of aldo-keto reductase 10.1038/s41598-017-00710-x1C32017

    • Author(s)
      Satoshi Endo, Sayaka Takada, Ryo P. Honda, Kathrin Muller, Jochen H. Weishaupt, Peter M. Andersen, Albert C. Ludolph, Yuji O. Kamatari, Toshiyuki Matsunaga, Kazuo Kuwata, Ossama El-Kabbani, Akira Ikari
    • Journal Title

      Chemico-Biological Interactions

      Volume: S0009-2797(16) Pages: 194-202

    • DOI

      10.1016/j.cbi.2016.12.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of compound selectivity of aldo-keto reductases using differential scanning fluorimetry2017

    • Author(s)
      Kabir Aurangazeb, Satoshi Endo, Naoki Toyooka, Mayuko Fukuoka, Kazuo Kuwata, and Yuji O. Kamatari
    • Journal Title

      Journal of Biochemistry

      Volume: 161 (2) Pages: 215-222

    • DOI

      10.1093/jb/mvw063

    • NAID

      40021133504

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effects of ligand binding on the stability of aldo-keto reductases (AKR)2016

    • Author(s)
      Kabir Aurangazeb, Ryo P. Honda, Yuji O. Kamatari, Satoshi Endo, Mayuko Fukuoka, and Kazuo Kuwata
    • Journal Title

      Protein Science

      Volume: 25(12) Issue: 12 Pages: 2132-41

    • DOI

      10.1002/pro.3036

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Application of high pressure NMR in the study of protein structure and dynamics2016

    • Author(s)
      H. Li,Y. O. Kamatari,R. Kitahara,K. Akasaka
    • Journal Title

      Chinese Journal of Magnetic Resonance

      Volume: 33 Pages: 1-26

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cavities and Excited States in Proteins.2015

    • Author(s)
      Li H, Kamatari YO.
    • Journal Title

      Subcell Biochem.

      Volume: 72 Pages: 237-257

    • DOI

      10.1007/978-94-017-9918-8_12

    • ISBN
      9789401799171, 9789401799188
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Synthesis of double-fluorescent labeled prion protein for FRET analysis.2015

    • Author(s)
      Hosokawa-Muto J, Yamaguchi K, Kamatari YO, Kuwata K.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 79 Issue: 11 Pages: 1802-1809

    • DOI

      10.1080/09168451.2015.1050991

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The structure and conformational switching of Rap1B2015

    • Author(s)
      H. Noguchi, T. Ikegami, A. Nagadoi, Y. O. Kamatari, S. Y. Park, J. R. H. Tame, S. Unzai
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 印刷中 Issue: 1 Pages: 46-51

    • DOI

      10.1016/j.bbrc.2015.04.103

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 標的蛋白質と低分子と低分子化合物との相互作用を検証する2018

    • Author(s)
      鎌足雄司
    • Organizer
      第7回岐阜構造生物学・医学・論理的創薬研究会シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 複数の抗原を特異的に認識する抗体G2の抗原認識機構の解明2018

    • Author(s)
      鎌足雄司
    • Organizer
      平成29年度生物物理学会中部支部講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] タンパク質の構造揺らぎと分子進化2017

    • Author(s)
      鎌足雄司
    • 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
    • Year and Date
      2017-03-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 複数の抗原を特異的に認識する抗体G2の抗原結合のよる構造及び揺らぎの変化2017

    • Author(s)
      鎌足雄司, 臼井大樹, Nuruddin Mahmud, 猪島康雄, 石黒直隆, 織田昌幸
    • Organizer
      平成28年度生物物理学会中部支部講演会
    • Place of Presentation
      名古屋
    • Year and Date
      2017-03-06
    • Related Report
      2016 Research-status Report
  • [Presentation] A three-in-one monoclonal antibody G2 recognizes completely different epitope sequences with high affinity2017

    • Author(s)
      Md. Nuruddin Mahmud, Masayuki Oda, Daiki Usui, Yasuo Inoshima, Naotaka Ishiguro, Yuji O. Kamatari
    • Organizer
      第55回日本生物物理学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Protein dynamics and molecular evolution2017

    • Author(s)
      Yuji O. Kamatari
    • Organizer
      9th International Meeting on Biomolecules under Pressure (IMBP2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interaction between Calmodulin and Bisphenol A2017

    • Author(s)
      Koichi Murayama, Yuji Kamatari, Satoshi Ohno, Masashi Sonoyama, Yoshiharu Sawada, Sadayuki Matusda
    • Organizer
      19th IUPAB congress and 11th EBSA congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ビスフェノールA結合に伴うアポ型カルモデュリンの構造変化の解析2017

    • Author(s)
      村山幸市, 鎌足雄司, 大野敏, 園山正史, 沢田義治, 松田禎行
    • Organizer
      第44回生体分子科学討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 複数のエピトープを認識するG2の1本鎖抗体の構造解析2016

    • Author(s)
      臼井大樹, 鎌足雄司, 稲葉理美, 織田昌幸
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      筑波
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of the third epitope recognized by multispecific antibody G22016

    • Author(s)
      Md. Nuruddin Mahmud, Yasuo Inoshima, Naotaka Ishiguro, Yuji O. Kamatari
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      筑波
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 示差走査型蛍光定量法を用いたアルドケト還元酵素の化合物選択性の評価2016

    • Author(s)
      アウロンゴゼブ コビル, 遠藤 智史, 豊岡 尚樹, 福岡 万佑子, 桑田 一夫, 鎌足 雄司
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      筑波
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] アルカン合成酵素のNMRと分子動力学シミュレーションによるダイナミクス解析2016

    • Author(s)
      末松佑麿,鎌足雄司,林勇樹,新井宗仁
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      筑波
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 複数の抗原を特異的に認識する抗体G2の抗原結合のよる構造及び揺らぎの変化2016

    • Author(s)
      鎌足雄司, 臼井大樹,石黒直隆, 織田昌幸
    • Organizer
      第55回NMR討論会
    • Place of Presentation
      広島
    • Year and Date
      2016-11-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 蛋白質の構造揺らぎと機能発現2016

    • Author(s)
      鎌足雄司
    • Organizer
      第17回若手NMR研究会
    • Place of Presentation
      箱根
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] Structural and dynamical changes of multispecific antibody G2 induced by binding of different antigens2016

    • Author(s)
      D. Usui, S. Shimizu, M. Oda, N. Ishiguro, Y. O. Kamatari
    • Organizer
      The 27th International Conference on Magnetic Resonance in Biological Systems (ICMRBS2016)
    • Place of Presentation
      京都
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Real-time in vitro conversion of prion protein detected by NMR2016

    • Author(s)
      K. Yamaguchi, Y. O. Kamatari, R. P. Honda, K. Kuwata
    • Organizer
      The 27th International Conference on Magnetic Resonance in Biological Systems (ICMRBS2016)
    • Place of Presentation
      京都
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] アルカン合成酵素ADのNMRと分子動力学シミュレーションによるダイナミクス解析2016

    • Author(s)
      末松佑麿,鎌足雄司,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
    • Year and Date
      2016-06-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Classification of anti-prion compounds based on the binding properties to prion proteins2016

    • Author(s)
      Y. O. Kamatari, K. Kuwata
    • Organizer
      PRION 2016 Tokyo in conjunction with Asian Pacific Prion Symposium 2016 (APPS2016)
    • Place of Presentation
      東京
    • Year and Date
      2016-05-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] タンパク質の構造揺らぎと機能発現2016

    • Author(s)
      鎌足雄司
    • Organizer
      第5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
    • Year and Date
      2016-03-10
    • Related Report
      2015 Research-status Report
  • [Presentation] タンパク質の構造揺らぎと機能発現2016

    • Author(s)
      鎌足雄司
    • Organizer
      津田沼分子科学フォーラム
    • Place of Presentation
      千葉工業大学
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] プリオンタンパク質を標的とした創薬におけるNMRの利用2015

    • Author(s)
      鎌足雄司
    • Organizer
      平成27年日本分光学会NMR部会集中講義
    • Place of Presentation
      名古屋大学
    • Year and Date
      2015-09-30
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 示差走査型蛍光定量法を用いたアルドケト還元酵素阻害剤の選択性の評価2015

    • Author(s)
      Y. O. Kamatari, A. Kabir, S. Endo, K. Kuwata,
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学
    • Year and Date
      2015-09-13
    • Related Report
      2015 Research-status Report
  • [Presentation] Spectroscopic and calorimetric analysis for conformational stability of c-Myb DNA-binding domain under different pH conditions2015

    • Author(s)
      S. Inaba, Y. O. Kamatari, H. Sekiguchi, H. Fukada, M. Oda,
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学
    • Year and Date
      2015-09-13
    • Related Report
      2015 Research-status Report
  • [Presentation] Strategy for elucidating abnormal structures of prion proteins using the double-fluorescent labeling method and FRET analysis2015

    • Author(s)
      Y. O. Kamatari, J. Hosokawa-Muto1, K. Yamaguchi, K. Kuwata,
    • Organizer
      Asian Pacific Prion Symposium 2015 (APPS2015)
    • Place of Presentation
      石川県立音楽堂
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural basis of cross-species prion transmission2015

    • Author(s)
      M. Tanaka, T. Shida, Y. O. Kamatari, K. Kuwata
    • Organizer
      Asian Pacific Prion Symposium 2015 (APPS2015)
    • Place of Presentation
      石川県立音楽堂
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cavity and hydration as a source of protein dynamics and function2015

    • Author(s)
      Y. O. Kamatari, H. Li
    • Organizer
      The International Society of Magnetic Resonance (ISMAR2015)
    • Place of Presentation
      上海
    • Year and Date
      2015-08-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 構造生物学的手法を用いた異種間プリオン蛋白質の相互作用解析2015

    • Author(s)
      志田俊信, 鎌足雄司, 山口芳樹, 桑田一夫, 田中元雅
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      徳島
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
  • [Remarks] 鎌足雄司

    • URL

      http://www1.gifu-u.ac.jp/~kamatari/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report 2015 Research-status Report
  • [Remarks] Yuji O Kamatari

    • URL

      https://www.researchgate.net/profile/Yuji_Kamatari

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Remarks] 鎌足雄司

    • URL

      http://researchmap.jp/kamatari/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report 2015 Research-status Report
  • [Remarks] 鎌足雄司

    • URL

      https://aris2.gifu-u.ac.jp/profile/ja.l41u26.html

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Remarks] Yuji O Kamatari

    • URL

      https://independent.academia.edu/YKamatari

    • Related Report
      2016 Research-status Report
  • [Remarks] Yuji O. Kamatari

    • URL

      https://www.researchgate.net/profile/Yuji_Kamatari

    • Related Report
      2015 Research-status Report
  • [Remarks] Yuji O. Kamatari

    • URL

      https://independent.academia.edu/YKamatari

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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