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Structural study for ligand recognition in G-protein coupled receptors

Research Project

Project/Area Number 17H05000
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Nishizawa Tomohiro  東京大学, 大学院理学系研究科(理学部), 助教 (80599077)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥26,260,000 (Direct Cost: ¥20,200,000、Indirect Cost: ¥6,060,000)
Fiscal Year 2019: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2018: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2017: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
KeywordsGPCR / X線結晶構造解析 / クライオ電子顕微鏡 / 構造生物学 / Gタンパク質共役型受容体 / 膜タンパク質 / 結晶構造解析 / Gタンパク質共役受容体 / 生物物理
Outline of Final Research Achievements

We revealed the structural basis for the ligand recognition and activation of G-protein coupled receptors (GPCRs), by solving the structures of various receptors. In this research, we have successfully obtained the structures of endothelin reeptor subtype-B (ETB), non-EDG LPA receptor LPA6, and pituitary adenylate cyclase-activating polypeptid (PACAP) receptor, and the structural comparison revealed similarity and diversity of GPCRs.

Academic Significance and Societal Importance of the Research Achievements

Gタンパク質共役型受容体(GPCR)はヒトを含む真核生物において細胞間でのシグナル伝達に関わる重要な膜タンパク質ファミリーである。既存の承認薬の30%はGPCRを標的するのに対して、いまだに構造の明らかになっていない受容体の数は多い。本研究では、血圧調節に関わるペプチド受容体であるエンドセリン受容体、細胞増殖などに関わる脂質受容体であるLPA6、神経における重要なシグナル伝達分子である下垂体アデニル酸シクラーゼ活性化ポリペプチド(PACAP)の受容体などに関して、構造を明らかにした。これらの情報は、構造をもとにした薬剤開発などにつながることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (12 results)

All 2020 2019 2018 2017 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (1 results)

  • [Journal Article] Cryo-EM structure of the human PAC1 receptor coupled to an engineered heterotrimeric G protein2020

    • Author(s)
      Kobayashi Kazuhiro、Shihoya Wataru、Nishizawa Tomohiro、Kadji Francois Marie Ngako、Aoki Junken、Inoue Asuka、Nureki Osamu
    • Journal Title

      Nature Structural & Molecular Biology

      Volume: 27 Issue: 3 Pages: 274-280

    • DOI

      10.1038/s41594-020-0386-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structures of human ETB receptor provide mechanistic insight into receptor activation and partial activation2018

    • Author(s)
      Shihoya Wataru、Izume Tamaki、Inoue Asuka、Yamashita Keitaro、Kadji Francois Marie Ngako、Hirata Kunio、Aoki Junken、Nishizawa Tomohiro、Nureki Osamu
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41467-018-07094-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] X-ray structures of endothelin ETB receptor bound to clinical antagonist bosentan and its analog2017

    • Author(s)
      Shihoya Wataru、Nishizawa Tomohiro、Yamashita Keitaro、Inoue Asuka、Hirata Kunio、Kadji Francois Marie Ngako、Okuta Akiko、Tani Kazutoshi、Aoki Junken、Fujiyoshi Yoshinori、Doi Tomoko、Nureki Osamu
    • Journal Title

      Nature Structural & Molecular Biology

      Volume: 24 Issue: 9 Pages: 758-764

    • DOI

      10.1038/nsmb.3450

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural insights into ligand recognition by the lysophosphatidic acid receptor LPA62017

    • Author(s)
      Taniguchi Reiya、Inoue Asuka、Sayama Misa、Uwamizu Akiharu、Yamashita Keitaro、Hirata Kunio、Yoshida Masahito、Tanaka Yoshiki、Kato Hideaki E.、Nakada-Nakura Yoshiko、Otani Yuko、Nishizawa Tomohiro、Doi Takayuki、Ohwada Tomohiko、Ishitani Ryuichiro、Aoki Junken、Nureki Osamu
    • Journal Title

      Nature

      Volume: 548 Issue: 7667 Pages: 356-360

    • DOI

      10.1038/nature23448

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure of the triose-phosphate/phosphate translocator reveals the basis of substrate specificity.2017

    • Author(s)
      Lee Y, Nishizawa T, Takemoto M, Kumazaki K, Yamashita K, Hirata K, Minoda A, Nagatoishi S, Tsumoto K, Ishitani R and Nureki O.
    • Journal Title

      Nature Plants.

      Volume: 3 Issue: 10 Pages: 825-832

    • DOI

      10.1038/s41477-017-0022-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural basis for xenobiotics extrusion by eukaryotic MATE transporter.2017

    • Author(s)
      Miyauchi H., Moriyama S., Kusakizako T., Kumazaki K., Ito K., Dohmae N., Nishizawa T., Miyaji T., Moriyama Y., Ishitani R., Nureki O.
    • Journal Title

      Nature Commun.

      Volume: 8 Issue: 1 Pages: 1633-1633

    • DOI

      10.1038/s41467-017-01541-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Structural biology of membrane transporters2019

    • Author(s)
      Tomohiro Nishizawa
    • Organizer
      Joint Annual Meeting of 71st JSCB & 19th PSSJ
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Membrane Transporter DynamicsRevealed by CryoEM2019

    • Author(s)
      Tomohiro Nishizawa
    • Organizer
      The 92nd Annual Meeting of The Japanese Biochemical Society
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Structural Insights Into Tetraspanin Function2019

    • Author(s)
      Tomohiro Nishizawa
    • Organizer
      Cold Spring Harbor Asia Conference CROSS-SCALE BIOLOGICAL STRUCTURE: FROM MACROMOLECULAR COMPLEXES & ORGANELLES TO CELLS & TISSUES
    • Related Report
      2019 Annual Research Report
  • [Presentation] X-ray crystal structures of the human endothelin type-B receptor (ETB)2017

    • Author(s)
      Tomohiro Nishizawa
    • Organizer
      15th Chinese Biophysics Congress (2017 ICBC)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] X線自由電子レーザーによって見えてきたチャネルロドプシンのイオン透過機構2017

    • Author(s)
      西澤知宏
    • Organizer
      第40回分子生物学会(ConBio 2017 )
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      https://www.s.u-tokyo.ac.jp/ja/press/2020/6729/

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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