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Structural basis for molecular mechanisms of membrane transporters

Research Project

Project/Area Number 24227004
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Biophysics
Research InstitutionThe University of Tokyo

Principal Investigator

Nureki Osamu  東京大学, 大学院理学系研究科(理学部), 教授 (10272460)

Co-Investigator(Kenkyū-buntansha) 伊藤 耕一  東京大学, 新領域創成科学研究科, 教授 (10262073)
MATURANA ANDRES  名古屋大学, 生命農学研究科, 准教授 (10452004)
Co-Investigator(Renkei-kenkyūsha) Maturana Andrés D.  名古屋大学, 生命農学研究科, 准教授 (10452004)
Project Period (FY) 2012-05-31 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥217,880,000 (Direct Cost: ¥167,600,000、Indirect Cost: ¥50,280,000)
Fiscal Year 2016: ¥31,460,000 (Direct Cost: ¥24,200,000、Indirect Cost: ¥7,260,000)
Fiscal Year 2015: ¥31,720,000 (Direct Cost: ¥24,400,000、Indirect Cost: ¥7,320,000)
Fiscal Year 2014: ¥31,720,000 (Direct Cost: ¥24,400,000、Indirect Cost: ¥7,320,000)
Fiscal Year 2013: ¥46,020,000 (Direct Cost: ¥35,400,000、Indirect Cost: ¥10,620,000)
Fiscal Year 2012: ¥76,960,000 (Direct Cost: ¥59,200,000、Indirect Cost: ¥17,760,000)
KeywordsX線結晶構造解析 / チャネル / トランスポーター / 遺伝学 / 電気生理学 / 膜輸送体 / リポソーム解析 / 計算機シミュレーション / 遺伝学解析 / パッチクランプ / 高分子構造・物性 / X線 / 生体分子 / タンパク質 / 薬理学
Outline of Final Research Achievements

Regarding ion channel, we solved high-resolution crystal structures of newly-identified Mg2+ channel MgtE, TRIC channel, P2X channel, and elucidated their substrate recognition mechanisms and gating mechanisms. For membrane transporters, we solved high-resolution crystal structures of Ca2+/H+ exchanger CAX, Fe2+ exporter FPN, sugar transporter SWEET, peptide transporter POT, amino acid exporter YddG, multi-drug exporter MATE, membrane protein integrator YidC to elucidate their substrate recognition mechanisms and transport mechanisms. We also solved high-resolution crystal structures of channel rhodopsin and light-driven Na+-pump KR2, which suggested how these rhodopsin channel/pump are gated upon light perception.

Assessment Rating
Verification Result (Rating)

A+

Assessment Rating
Result (Rating)

A+: Progress in the research exceeds the initial goal. More than expected research results are expected.

Report

(8 results)
  • 2017 Research Progress Assessment (Verification Result) ( PDF )
  • 2016 Final Research Report ( PDF )
  • 2015 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (32 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 4 results) Presentation (18 results) (of which Int'l Joint Research: 2 results,  Invited: 12 results) Remarks (3 results)

  • [Journal Article] Structural Insights into Divalent Cation Modulations of ATP-Gated P2X Receptor Channels2016

    • Author(s)
      Kasuya, G., Y. Fujiwara, M. Takemoto, N. Dohmae, Y. Nakada-Nakura, R. Ishitani, M. Hattori, and O. Nureki
    • Journal Title

      Cell Report

      Volume: 14 Issue: 4 Pages: 932-944

    • DOI

      10.1016/j.celrep.2015.12.087

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural basis for amino-acid export by DMT superfamily transporter YddG2016

    • Author(s)
      H. Tsuchiya, S. Doki, M. Takemoto, T. Ikuta, T. Higuchi, K. Fukui, Y. Usuda, E. Tabuchi, S. Nagatoishi, K. Tsumoto, T. Nishizawa, K. Ito, N. Dohmae, R. Ishitani and O. Nureki
    • Journal Title

      Nature

      Volume: 534 Issue: 7607 Pages: 417-420

    • DOI

      10.1038/nature17991

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin2015

    • Author(s)
      Taniguchi R, Kato HE, Font J, Deshpande CN, Wada M, Ito K, Ishitani R, Jormakka M, Nureki O
    • Journal Title

      Nat. Commun.

      Volume: 6 Issue: 1 Pages: 8545-8545

    • DOI

      10.1038/ncomms9545

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structural basis for Sec-independent membrane protein insertion by YidC.2014

    • Author(s)
      Kumazaki, K., Chiba, S., Takemoto, M., Furukawa, A., Nishiyama, K., Sugano, Y., Mori, T., Dohmae, N., Hirata, K., Nakada-Nakura, Y., Maturana, A.D., Tanaka, Y., Mori, H., Sugita, Y., Arisaka, F., Ito K., Ishitani, R., Tsukazaki, T. and Nureki, O.
    • Journal Title

      Nature

      Volume: 509 Issue: 7501 Pages: 516-520

    • DOI

      10.1038/nature13167

    • Related Report
      2014 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Crystal structure of a claudin provides insight into the architecture of tight junctions2014

    • Author(s)
      Suzuki H, Nishizawa T, Tani K, Yamazaki Y, Tamura A, Ishitani R, Dohmae N, Tsukita S, Nureki O, Fujiyoshi Y
    • Journal Title

      Science

      Volume: 344 Issue: 6181 Pages: 304

    • DOI

      10.1126/science.1248571

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg(2+) channel MgtE2014

    • Author(s)
      Takeda H, Hattori M, Nishizawa T, Yamashita K, Shah ST, Caffrey M, Maturana AD, Ishitani R, Nureki O
    • Journal Title

      Nat Commun

      Volume: 5 Issue: 1 Pages: 5374-5374

    • DOI

      10.1038/ncomms6374

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural basis for the drug extrusion mechanism by a MATE multidrug transporter2013

    • Author(s)
      Y・ Tanaka, C・J・ Hipolito, A・D・ Maturana, K・ Ito, T・ Kuroda, T・ Higuchi, T・ Katoh, H・E・ Kato, M・ Hattori, K・ Kumazaki, T・ Tsukazaki, R・ Ishitani, H・ Suga, O・ Nureki
    • Journal Title

      Nature

      Volume: 496 Issue: 7444 Pages: 247-51

    • DOI

      10.1038/nature12014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT.2013

    • Author(s)
      Doki, S., Kato, H. E., Solcan, N., Iwaki, M., Koyama, M., Iwase, N., Tsukazaki, T., Sugita, Y., Kandori, H., Newstead, S., Ishitani, R., and Nureki, O.
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States

      Volume: 110 Issue: 28 Pages: 11343-11348

    • DOI

      10.1073/pnas.1301079110

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural Basis for the Counter-Transport Mechanism of a H+/Ca2+ Exchanger2013

    • Author(s)
      Nishizawa T, Kita S, Maturana AD, Furuya N, Hirata K, Kasuya G, Ogasawara S, Dohmae N, Iwamoto T, Ishitani R, Nureki O
    • Journal Title

      Science

      Volume: 341 Issue: 6142 Pages: 168-172

    • DOI

      10.1126/science.1239002

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A macrocyclic peptide that serves as a cocrystallization ligand and inhibits the function of a MATE family transporte2013

    • Author(s)
      C・J・ Hipolito, Y・Tanaka, T・ Katoh, O・ Nureki, H・ Suga
    • Journal Title

      Molecules

      Volume: 18 Issue: 9 Pages: 10514-30

    • DOI

      10.3390/molecules180910514

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function of Zucchini endoribonuclease in piRNA biogenesis.2012

    • Author(s)
      Hiroshi Nishimasu, Hirotsugu Ishizu
    • Journal Title

      Nature

      Volume: 491 Issue: 7423 Pages: 284-287

    • DOI

      10.1038/nature11509

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] High-resolution X-ray Crystallography of Membrane Proteins and Molecular Mechanisms of Membrane Transporters2016

    • Author(s)
      O. Nureki
    • Organizer
      16th International Conference on the Crystallization of Biological Macromolecules
    • Place of Presentation
      Praha(Czech Republic)
    • Year and Date
      2016-07-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] High-resolution X-ray Crystallography of Membrane Proteins and Molecular Mechanisms of Membrane Transporters2016

    • Author(s)
      O. Nureki
    • Organizer
      KVA-JSPS seminar
    • Place of Presentation
      Stockholm(Sweden)
    • Year and Date
      2016-06-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 薬剤などの輸送に働くトランスポーターの分子機構2016

    • Author(s)
      O. Nureki
    • Organizer
      千里ライフサイエンスセミナー
    • Place of Presentation
      千里ライフセンター(大阪府豊中市)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Molecular Processes Underlying the Early Stages of Channel Opening in Channelrhodopsin and its Structure-based Engineering2014

    • Author(s)
      O. Nureki
    • Organizer
      16th International Conference on Retinal Proteins -ICRP2014-
    • Place of Presentation
      Nagahama, Japan
    • Year and Date
      2014-10-05 – 2014-10-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular Processes Underlying the Early Stages of Channel Opening in Channelrhodopsin and its Structure-based Engineering2014

    • Author(s)
      O. Nureki
    • Organizer
      Membrane Transport and Communication
    • Place of Presentation
      Frankfurt, Germany
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Molecular Mechanisms of Membrane Channel and Transporter2014

    • Author(s)
      O. Nureki
    • Organizer
      Congress and General Assembly of the International Union of Crystallography
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2014-08-05 – 2014-08-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Molecular Basis of Channelrhodopsin and Its Variant Design2014

    • Author(s)
      O. Nureki
    • Organizer
      Gordon Research Conference: Photosensory Receptors & Signal Transduction
    • Place of Presentation
      Lucca, Italy
    • Year and Date
      2014-04-06 – 2014-04-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Structure-based drug design using chemical compound and peptide2013

    • Author(s)
      O. Nureki
    • Organizer
      The 11th International Symposium for Future Drug Discovery and Medical Care
    • Place of Presentation
      Hokkaido
    • Year and Date
      2013-08-01 – 2013-08-02
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Structural basis for light-gated cation conductance by channelrhodopsin2013

    • Author(s)
      O. Nureki
    • Organizer
      Therapeutics Discovery Symposia-2013
    • Place of Presentation
      Boston, USA
    • Year and Date
      2013-05-01 – 2013-05-02
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Structural basis of molecular mechanism of ATX/Enpp2

    • Author(s)
      濡木理
    • Organizer
      The 1st International Symposium on Lipid Mediators
    • Place of Presentation
      九州大学(福岡)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 慢性炎症の構造的基盤

    • Author(s)
      濡木理
    • Organizer
      千里ライフサイエンスセミナー (炎症の慢性化と疾患)
    • Place of Presentation
      千里ライフサイエンスセミナー(大阪)
    • Related Report
      2012 Annual Research Report
  • [Presentation] MATE輸送体による動的な薬剤排出機構

    • Author(s)
      濡木理
    • Organizer
      第35回日本分子生物学会 ワークショップ
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] A20タンパク質による直鎖状ユビキチンを介したNFkBシグナルの制御機構

    • Author(s)
      濡木理
    • Organizer
      第85回日本生化学会 シンポジウム
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Structural basis for light-gated cation conductance by channelrhodopsin

    • Author(s)
      濡木理
    • Organizer
      Therapeutics Discovery Symposia-2013
    • Place of Presentation
      Hilton Garden Inn(BOSTON,USA)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Structure and function of Zucchini endoribonuclease in piRNA biogenesis

    • Author(s)
      濡木理
    • Organizer
      American Crystallographic meeting
    • Place of Presentation
      SHERATON WAIKIKI(HONOLULU,USA)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Sructure-based drug design using small molecule and peptide

    • Author(s)
      濡木理
    • Organizer
      第11回未来創薬・医療イノベーション拠点形成シンポジウム
    • Place of Presentation
      北海道大学(北海道)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Structural basis for drug extrusion mechanism by MATE transporter and its inhibitor design

    • Author(s)
      濡木理
    • Organizer
      第86回日本生化学会大会 シンポジウム
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 多剤排出トランスポーターの構造解析とペプチド性インヒビターの創出

    • Author(s)
      濡木理
    • Organizer
      千里ライフサイエンスセミナー (創薬関連分子の構造生物学の最前線)
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Related Report
      2012 Annual Research Report
  • [Remarks] 血管収縮因子エンドセリンの受容体初期活性化機構を解明

    • URL

      http://www.spring8.or.jp/ja/news_publications/press_release/2016/160906/

    • Related Report
      2015 Annual Research Report
  • [Remarks] アミノ酸排出輸送タンパク質YddGがアミノ酸分子を輸送するしくみ

    • URL

      http://www.s.u-tokyo.ac.jp/ja/press/2016/4858/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 濡木研究室ホームページ

    • URL

      http://www.nurekilab.net/

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report

URL: 

Published: 2012-11-27   Modified: 2019-07-29  

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