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Structural basis for molecular mechanisms of substrate recognition and transport regulation by membrane transporters

Research Project

Project/Area Number 20227003
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Structural biochemistry
Research InstitutionThe University of Tokyo (2009-2012)
Tokyo Institute of Technology (2008)

Principal Investigator

NUREKI Osamu  東京大学, 理学(系)研究科(研究院), 教授 (10272460)

Co-Investigator(Kenkyū-buntansha) MATURANA Andres  名古屋大学, 農学部, 准教授 (10452004)
ITO Koichi  東京大学, 新領域創成科学研究科, 教授 (10262073)
Project Period (FY) 2008-05-12 – 2013-03-31
Project Status Declined (Fiscal Year 2012)
Budget Amount *help
¥207,870,000 (Direct Cost: ¥159,900,000、Indirect Cost: ¥47,970,000)
Fiscal Year 2012: ¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000)
Fiscal Year 2011: ¥53,040,000 (Direct Cost: ¥40,800,000、Indirect Cost: ¥12,240,000)
Fiscal Year 2010: ¥38,350,000 (Direct Cost: ¥29,500,000、Indirect Cost: ¥8,850,000)
Fiscal Year 2009: ¥36,140,000 (Direct Cost: ¥27,800,000、Indirect Cost: ¥8,340,000)
Fiscal Year 2008: ¥52,910,000 (Direct Cost: ¥40,700,000、Indirect Cost: ¥12,210,000)
KeywordsX 線結晶構造解析 / チャネル / トランスポーター / 電気生理学解析 / 遺伝学解析 / X線結晶構造解析 / 計算機シミュレーション / パッチクランプ / 膜輸送体 / 電気生理学 / 遺伝学
Research Abstract

Membrane transporters maintain the intracellular circumstances by strictly regulating the import and export of metal ions, sugars, metabolites and drugs etc. To elucidate (A) how the transporters drive their transport, (B) how the transporters exclusively select their specific substrates and (C) how the transporters regulate their transporting activities at at an atomic resolution, we performed (1) structure determination by X-ray crystallography, (2) dynamic property analysis by MD simulation and (3) in vivo and in vitro complementary experiments, focusing on ion transporters of magnesium, iron and heavy metals, light-gated cation channels, protein transporters, peptide transporter and multidrug transporters. Especially, we uncovered the essential molecular mechanism of membrane transport by comparing and integrating the functional mechanisms of transporters specific for various kinds of target solutes.

Assessment Rating
Verification Result (Rating)

A+

Report

(5 results)
  • 2013 Research Progress Assessment (Verification Result) ( PDF )
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report   Self-evaluation Report ( PDF )
  • Research Products

    (51 results)

All 2012 2011 2010 2009 2008 Other

All Journal Article (25 results) (of which Peer Reviewed: 19 results) Presentation (16 results) (of which Invited: 5 results) Book (8 results) Remarks (2 results)

  • [Journal Article] Crystal structure of the channelrhodopsin light-gated cation channel2012

    • Author(s)
      Hideaki E.Kato, Feng Zhang, Ofer Yizhar, Charu Ramakrishnan, Tomohiro Nishizawa, Kunio Hirata, Jumpei Ito, Yusuke Aita, Tomoya Tsukazaki, Shigehiko Hayashi, Peter Hegemann, Andres D.Maturana, Ryuichiro Ishitani, Karl Deisseroth, Osamu Nureki
    • Journal Title

      Nature

      Volume: 482 Issue: 7385 Pages: 369-374

    • DOI

      10.1038/nature10870

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function of a membrane component SecDF that enhances protein export2011

    • Author(s)
      T.Tsukazaki,H.Mori,Y.Ech izen,R.Ishitani, S.Fukai,T.Tanaka,A.Perederina,D.G.Vassylyev, T.Koh no,A.D.Maturana, K.Itoand O.
    • Journal Title

      NurekiNature

      Volume: 474 Pages: 235-238

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of autotaxin and insig ht into GPCR activation by lipid mediat ors2011

    • Author(s)
      H. Nishimasu, S.Okudaira, K.Ha ma, E.Mihara, N.Dohmae, A.Inoue, R.Ishitani, J.Takagi, J.Aokiand O.
    • Journal Title

      NurekiNat.Struct.Mol.Biol

      Volume: 18 Pages: 205-212

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] tructure and function of SecDF, a protein export-enhancing membrane component2011

    • Author(s)
      Tsukazaki, T., et al
    • Journal Title

      Nature

      Volume: 475 Issue: 7350 Pages: 235-238

    • DOI

      10.1038/nature09980

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray diffraction of the first periplasmic domain of SecDF, a translocon-associated membrane protein, from Thermus thermophilus2011

    • Author(s)
      Y. Echizen, T. Tsukazaki, N. Dohmae, R. Ishitani and O. Nureki
    • Journal Title

      Acta Crystallogr. F

      Volume: 67 Issue: 11 Pages: 1367-1370

    • DOI

      10.1107/s1744309111031885

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function of a membrane component SecDF that enhances protein export2011

    • Author(s)
      T.Tsukazaki(8名), A.Maturana, K.Ito, O.Nureki
    • Journal Title

      Nature in press

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Crystal structure of autotaxin and insight into GPCR activation by lipid mediators2011

    • Author(s)
      S.Nishimasu, et al.
    • Journal Title

      Nat.Struct.Mol.Biol.

      Volume: 18 Pages: 3912-3917

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function of a membrane component SecDF that enhances protein export2011

    • Author(s)
      T.Tsukazaki, et al.
    • Journal Title

      Nature

      Volume: (掲載確定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms underlying the ea rly stage of protein translocation throug h the Sec translocon2010

    • Author(s)
      T.Mori,R..Ishita ni,T. Tsukazaki, O,Nureki and Y
    • Journal Title

      Sug itaBiochemistry

      Volume: 49 Pages: 945-950

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms underlying the early stage of protein translocation through the Sec translocon.2010

    • Author(s)
      T.Mori, et al.
    • Journal Title

      Biochemistry

      Volume: 49 Pages: 945-950

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mg^2+-dependent gating of bacterial MgtE channel underlies Mg^2+ homeostasis2009

    • Author(s)
      M. Hattori, N. Iwase, N. Furuya, Y. Tana ka, T. Tsukazaki, R. Ishitani, M. E. Ma guire, K. Ito, A. Maturana and O
    • Journal Title

      Nure ki EMBO J

      Volume: 28 Pages: 3602-3612

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for translational fidelity ensured by tRNA lysidine synthetase2009

    • Author(s)
      K. Nakanishi, L. Bonnefond, S. Kimura, T. Suzuki, R. Ishitani and O
    • Journal Title

      Nureki.Nature

      Volume: 461 Pages: 1144-1148

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis of novel interactions bet ween the small-GTPase and GDI-like do mains in prokaryotic FeoB iron transport er2009

    • Author(s)
      M. Hattori, Y. Jin, H. Nishimasu, Y. Tanaka, M. Mochizuki, T. Uchiumi, R. Ishitani, K. Ito and O.
    • Journal Title

      Nureki.Structure

      Volume: 17 Pages: 1345-1355

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray dif fraction analysis of the truncated cytosol ic domain of the iron transporter FeoB2009

    • Author(s)
      Y. Jin, M. Hattori, H. Nisimasu, R. Is hitani and O.
    • Journal Title

      NurekiActa.Crystallogr.Sect.F

      Volume: 65 Pages: 784-787

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tuberous Sclerosis Tumor Suppressor C omplex-like Complexes Act as GTPase-a ctivating Proteins for Ral GTPases2009

    • Author(s)
      R. Shirakawa, S.Fukai, M.Kawato, T.Hi gashi, H. Kondo, T.Ikeda, E.Nakayam a, K.Okawa, O.Nureki, T.Kimura, T.Kita and H. Horiuchi.J
    • Journal Title

      Biol. Chem

      Volume: 284 Pages: 21580-21588

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the cytosolic domainof the cation diffusion facilitator famil y protein2009

    • Author(s)
      T.Higuchi, M.Hattori, Y.Tanaka, R. Ishitani and O
    • Journal Title

      Nureki.Proteins

      Volume: 76 Pages: 768-771

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of orthogonality2009

    • Author(s)
      K.Nozawa, P.O'Donogh ue, S.Gundllapalli, Y.Araiso, R. Ishita ni, T. Umehara, D.S^^oll and O.Nureki
    • Journal Title

      Nature

      Volume: 457 Pages: 1163-1167

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mg^<2+>-dependent gating of bacterial MgtE channel underlies Mg^<2+> homeostasis2009

    • Author(s)
      M.Hattori(6名), K.Ito, A.Maturana, O.Nureki
    • Journal Title

      EMBO J. 28

      Pages: 3602-3612

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Structural basis of novel interactions between the small-GTPase and GDI-like domains in prokaryotic FeoB iron transporter.2009

    • Author(s)
      M.Hattori(6名), K.Ito, O.Nureki.
    • Journal Title

      Structure 17

      Pages: 1345-1355

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Crystal structure of the cytosolic domain of the cation diffusion facilitator family protein.2009

    • Author(s)
      T.Higuchi(3名), O.Nureki.
    • Journal Title

      Proteins 76

      Pages: 768-771

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Conformational transition of Sec machi nery inferred from bacterial SecYE struc tures2008

    • Author(s)
      T.Tsukazaki, H. Mori, S.Fukai, R.Ishitani, T.Mori, N.Dohmae, A.P erederina, Y.Sugita, D.G.Vassylyev, K.Ito and O.Nureki
    • Journal Title

      Nature

      Volume: 455 Pages: 988-91

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mg^2+-sensing mechanism of Mg2+ trans porter MgtE probed by molecular dyna mics study2008

    • Author(s)
      R.Ishitani, Y.Sugita, N.Dohmae, N.Furuya, M.Hattori, and O.
    • Journal Title

      Nureki Proc. Natl. Acad. USA

      Volume: 105 Pages: 15393-15398

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of platelet dense granule se cretion by the Ral GTPase-Exocyst path way2008

    • Author(s)
      M.kawato, R.Shirakawa, H.Kon do, T.Higashi, T. Ikeda, K.Okawa, S.Fukai, O.Nureki, T.Kita, H.Horiuchi J
    • Journal Title

      Biol. Chem

      Volume: 283 Pages: 166-174

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conformational transition of Sec machinery inferred from bacterial SecYE structures2008

    • Author(s)
      T.Tsukazaki(9名), O.Nureki.
    • Journal Title

      Nature 455

      Pages: 988-991

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Mg^<2+>-sensing mechanism of Mg^<2+> transporter MgtE probed by molecular dynamics study2008

    • Author(s)
      R.Ishitani(4名), O.Nureki
    • Journal Title

      Proc.Natl.Acad.USA. 105

      Pages: 15393-15398

    • Related Report
      2010 Self-evaluation Report
  • [Presentation] Structure of complexes of multidrug exporter and screened cyclic peptides for structure-based inhibitor design2012

    • Author(s)
      O. Nureki
    • Organizer
      Gordon Research Conference “Ligand Recognition & Molecular Gating”
    • Place of Presentation
      Ventura, CA, USA
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Structural basis for light-gated cation conductance by channelrhodopsin2012

    • Author(s)
      O. Nureki
    • Organizer
      15th International Conference on Retinal Proteins
    • Place of Presentation
      Ascona, Switzerland
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] The 2011 International Symposium onAminoacyl-tRNA Synthetases2011

    • Author(s)
      O.Nureki
    • Organizer
      Archaeal elongation factor acts an omnipotent carrier GTPase in translational elongation, termination and mRNA syrveillance
    • Place of Presentation
      Snowbird, Utah, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Basis for Dynamic Protein Translocation Across Plasma membrane by Sec Machinery2011

    • Author(s)
      Osamu Nureki
    • Organizer
      Symposium of Biomolecular Structure and Dynamics
    • Place of Presentation
      KAIST, Daejeon, Korea
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Structural Basis for Dynamic Protein Translocation Across Plasma membrane by Sec Machinery2011

    • Author(s)
      Osamu Nureki
    • Organizer
      Taiwan-Japan Joint Seminar on Crystallography
    • Place of Presentation
      Taipei, Taiwan
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Structure and functional mechanism of membrane transporters: Structure determination from nano-crystals2011

    • Author(s)
      O. Nureki, H. Kato, Y. Tanaka, S. Douki, T. Nishizawa, T. Tsukazaki, R. Ishitani
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      Yokohama,Kanagawa, Japan
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Structural basis for the gating mechanism of cation and polypeptide channels2010

    • Author(s)
      O.Nureki
    • Organizer
      The 2^<nd> Annual Meeting of Structural Biology of Membrane Proteins
    • Place of Presentation
      Basel, Switzerland
    • Year and Date
      2010-01-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] The 10th Conference of the Asian Crystallographic Association2010

    • Author(s)
      O.Nureki
    • Organizer
      Structural analysis of bacterial Sec translocon machinery
    • Place of Presentation
      Busan,Korea
    • Related Report
      2011 Final Research Report
  • [Presentation] The 2 nd Annual Meeting of Structural Biology of Membrane Proteins2010

    • Author(s)
      O.Nureki
    • Organizer
      Structural basis for the gating mechanism of cation and polypeptide channels
    • Place of Presentation
      Basel, Switzerland
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural analysis of bacterial Sec translocon machinery2010

    • Author(s)
      T.Tsukazaki, H.Mori, K.Ito, O.Nureki
    • Organizer
      The 10^<th> Conference of the Asian Crystallographic Association
    • Place of Presentation
      Busan, Korea
    • Related Report
      2010 Annual Research Report 2010 Self-evaluation Report
  • [Presentation] 11th International Congress on Amino Acids, Peptides and Proteins2009

    • Author(s)
      O.Nureki
    • Organizer
      Genetic code expansion by non-canonical tRNA synthetases
    • Place of Presentation
      Vienna,Austria
    • Year and Date
      2009-08-06
    • Related Report
      2011 Final Research Report
  • [Presentation] VIII European Symposium of The Protein Society2009

    • Author(s)
      O. Nureki
    • Organizer
      Multiple conformational states of Sec machinery components implicated from bacterial SecYE crystal structure
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2009-06-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Multiple conformational states of Sec machinery components implicated from bacterial SecYE crystal structure2009

    • Author(s)
      O.Nureki
    • Organizer
      VIII European Symposium of The Protein Society
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2009-06-16
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] The Joint 2nd Pacific Rim International Conference on Protein Science2008

    • Author(s)
      O. Nureki
    • Organizer
      Gating control; mechanism of magnesium transporter MgtE
    • Place of Presentation
      Cairns, Australia
    • Related Report
      2011 Final Research Report
  • [Presentation] Gating control ; mechanism of magnesium transporter MgtE2008

    • Author(s)
      O.Nureki
    • Organizer
      The Joint 2^<nd> Pacific Rim International Conference on Protein Science
    • Place of Presentation
      Cairns, Australia
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] Crystal structure of the MgtE Mg^<2+> transporter2008

    • Author(s)
      O.Nureki
    • Organizer
      Gordon Research Conference-Magnesium in Biochemical Processes & Medicine
    • Place of Presentation
      Ventura, CA, USA
    • Related Report
      2010 Self-evaluation Report
  • [Book] タンパク質を膜透過させる分子装置2011

    • Author(s)
      塚崎智也
    • Publisher
      濡木理化学工業
    • Related Report
      2011 Final Research Report
  • [Book] タンパク質を膜透過させる分子装置2011

    • Author(s)
      塚崎智也
    • Total Pages
      10
    • Publisher
      細胞工学
    • Related Report
      2011 Annual Research Report
  • [Book] 細胞工学2011

    • Author(s)
      塚崎智也, 濡木理
    • Publisher
      タンパク質を膜透過させる分子装置 印刷中
    • Related Report
      2010 Annual Research Report
  • [Book] ピロリジン翻訳直行性のメカニズム2010

    • Author(s)
      野澤佳世,石谷隆一郎
    • Publisher
      濡木理生化学
    • Related Report
      2011 Final Research Report
  • [Book] ピロリジルtRNA合成における翻訳の直交性の分子構造基盤2009

    • Author(s)
      濡木理
    • Publisher
      蛋白質核酸酵素5
    • Related Report
      2011 Final Research Report
  • [Book] CCA付加反応のダイナミクス2008

    • Author(s)
      濡木理
    • Publisher
      生化学
    • Related Report
      2011 Final Research Report
  • [Book] マグネシウムトランスポーターによる細胞内マグネシウムバランス調節機構2008

    • Author(s)
      濡木理,服部素之,石谷隆一郎
    • Publisher
      生化学
    • Related Report
      2011 Final Research Report
  • [Book] MgtEトランスポーターによるMg2+のホメオスタシス機構2008

    • Author(s)
      服部素之,濡木理
    • Publisher
      蛋白質核酸酵素
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.nurekilab.net/

    • Related Report
      2011 Final Research Report
  • [Remarks] 濡木研究室ホームページ

    • URL

      http://www.nurekilab.net/

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2019-07-29  

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