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Structural biology of secondary active transporters

Research Project

Project/Area Number 22687007
Research Category

Grant-in-Aid for Young Scientists (A)

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

Principal Investigator

ISHITANI Ryuichiro  東京大学, 大学院・理学系研究科, 准教授 (90361568)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2011: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2010: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
KeywordsX 線結晶構造解析 / 膜蛋白質 / 膜輸送体 / ドラッグデリバリー / 多剤排出因子 / X線結晶構造解析
Research Abstract

Active transporters are membrane protein that mediates translocation of various substrates across the biological membrane by consuming energy, and thus are important for maintaining intra- and extracellular environment. The secondary active transporters translocate the small molecules, including amino acids, nucleic acids, sugars and drags,by utilizing the electrochemical gradient of H+ or Na+ across the membrane. In this project, we focused on the three important secondary active transporters, multidrug efflux transporter MATE, Ca2+/cation exchanger CaCA, and oligopeptide symporter POT, and performed structural and functional analyses of these targets.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report

Research Products

(45 results)

All 2013 2012 2011 2010 Other

All Journal Article Presentation Book Remarks

  • [Journal Article] Structural Basis for the Counter-Transport Mechanism of a H+/Ca2+ Exchanger.2013

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

      Science

      Volume: (掲載決定)

    • Related Report
      2012 Final 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 HE, Solcan N, Iwaki M, Koyama M, Iwase N, Tsukazaki T, Hattori M, Sugita Y, Kandori H, Newstead S, Ishitani R ,Nureki O.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: (掲載決定)

    • NAID
      130003391407
    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Screening and X-Ray Crystal Structure-based Optimization of Autotaxin (ENPP2) Inhibitors, Using a Newly Developed Fluorescence Probe.2013

    • Author(s)
      Kawaguchi M, Okabe T, Okudaira S, Nishimasu H, Ishitani R, Kojima H, Nureki O, Aoki J, Nagano T.
    • Journal Title

      ACS Chem Biol

      Volume: (掲載決定)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the drug extrusion mechanism by a MATE multidrug transporter.2013

    • Author(s)
      Tanaka Y, Hipolito CJ, Maturana AD, Ito K, Kuroda T, Higuchi T, Katoh T, Kato HE, Hattori M, Kumazaki K, Tsukazaki T, Ishitani R, Suga H, Nureki O.
    • Journal Title

      Nature

      Volume: 496 Pages: 247-251

    • NAID
      120005716854
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of Cex1p reveals the mechanism of tRNA trafficking between nucleus and cytoplasm2013

    • Author(s)
      Nozawa K, Ishitani R, Yoshihisa T, Sato M, Arisaka F, Kanamaru S, Dohmae N, Mangroo D, Senger B, Becker HD, Nureki O
    • Journal Title

      Nucleic Acids Res

      Volume: 41 Pages: 3901-3901

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the novel mechanism of drug extrusion by a MATE multidrug transporter2013

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

      Nature

      Volume: 491 Pages: 284-284

    • DOI
      10.1038/nature11509
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Backbone resonance assignments for the cytoplasmic region of the Mg(2+) transporter MgtE in the Mg(2+)-unbound state.2013

    • Author(s)
      Maruyama T, Imai S, Osawa M, Hattori M, Ishitani R, Nureki O, Shimada I.
    • Journal Title

      Biomol NMR Assign.

      Volume: 7 Pages: 93-6

    • DOI
      10.1007/s12104-012-9385-y
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function of Zucchini endoribonuclease in piRNA biogenesis.2012

    • Author(s)
      Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J, Ishitani R, Siomi H, Siomi MC, Nureki O.
    • Journal Title

      Nature

      Volume: 491 Pages: 284-287

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Dynamics Simulation of Autotaxin: Roles of the Nuclease-like Domain and the Glycan Modification.2012

    • Author(s)
      Koyama M, Nishimasu H, Ishitani R , Nureki O.
    • Journal Title

      J Phys Chem B

      Volume: 116 Pages: 11798-11808

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for trans lation termination by archaeal RF1 and GTP-bound EF1α complex.2012

    • Author(s)
      Kobayashi K, Saito K, Ishitani R , Ito K, Nureki O.
    • Journal Title

      Nucleic Acids Res

      Volume: 40 Pages: 9319-9328

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spatial distribution of cytoplasmic domains of the Mg2+-transporter MgtE, in a solution lacking Mg2+, revealed by paramagnetic relaxation enhancement.2012

    • Author(s)
      Imai S, Maruyama T, Osawa M, Hattori M, Ishitani R, Nureki O, Shimada I.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1824 Pages: 1129-1135

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the channelrhodopsin light-gated cation channel.2012

    • Author(s)
      Kato HE, Zhang F, Yizhar O, RamakrishnanC, Nishizawa T, Hirata K, Ito J, Aita Y, Tsukazaki T, Hayashi S, Hegemann P, Maturana AD, Ishitani R, Deisseroth K, Nureki O.
    • Journal Title

      Nature

      Volume: 482 Pages: 369-374

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression, purification, crystallization and preliminary X-ray crystallographic analysis of Zucchini from Drosophila melanogaster2012

    • Author(s)
      Fukuhara S, Nishimasu H, Bonnefond L, Matsumoto N, Ishitani R, Nureki O
    • Journal Title

      Acta Crystallogr Sect F Struct Biol Cryst Commun

      Volume: F68 Pages: 1346-1346

    • DOI
      10.1107/s1744309112038936
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The tRNA recognition mechanism of folate/FAD-dependent tRNA methyltransferase (TrmFO).2012

    • Author(s)
      Yamagami R, Yamashita K, Nishimasu H, Tomikawa C, Ochi A, Iwashita C, Hirata A, Ishitani R, Nureki O, Hori H
    • Journal Title

      Journal of Biological Chemistry

      Volume: 287 Pages: 42480-42480

    • DOI
      10.1074/jbc.m112.390112
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation.2012

    • Author(s)
      Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, Kamei K, Ma A, Iwai K, Nureki O
    • Journal Title

      EMBO J

      Volume: 31 Pages: 3856-3856

    • DOI
      10.1038/emboj.2012.241
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin2012

    • Author(s)
      Kato K, Nishimasu H, Okudaira S, Mihara E, Ishitani R, Takagi J, Aoki J, Nureki O
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109 Pages: 16876-16876

    • DOI
      10.1073/pnas.1208017109
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular dynamics simulation of Autotaxin : roles of the nuclease-like domain and the glycan modification2012

    • Author(s)
      Michio Koyama, Hiroshi Nishimasu, Ryuichiro Ishitani, Osamu Nureki
    • Journal Title

      J Phys Chem B

      Volume: 116 Pages: 11798-11798

    • DOI
      10.1021/jp303198u
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simplification of the genetic code: restricted diversity of genetically encoded amino acids2012

    • Author(s)
      Kawahara-Kobayashi A, Masuda A, Araiso Y, Sakai Y, Kohda A, Uchiyama M, Asami S, Matsuda T, Ishitani R, Dohmae N, Yokoyama S, Kigawa T, Nureki O, Kiga D
    • Journal Title

      Nucleic Acids Research

      Volume: 40 Pages: 10576-10576

    • DOI
      10.1093/nar/gks786
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for translation termination by archaeal RF1 an GTP-bound EF1α complex.2012

    • Author(s)
      Kan Kobayashi, Kazuki Saito, Ryuichiro Ishitani, Koichi Ito, Osamu Nureki
    • Journal Title

      Nucleic Acids Res

      Volume: 40 Pages: 9319-28

    • DOI
      10.1093/nar/gks660
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression, purification, crystallization and preliminary X-ray crystallographic analysis of Enpp12012

    • Author(s)
      Kato K, Nishimasu H, Mihara E, Ishitani R, Takagi J, Aoki J, Nureki O
    • Journal Title

      Acta Crystallographica Section F

      Volume: F68 Pages: 778-778

    • DOI
      10.1107/s1744309112019306
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatial distribution of cytoplasmic domains of the Mg(2+)-transporter MgtE, in a solution lacking Mg(2+), revealed by paramagnetic relaxation enhancement.2012

    • Author(s)
      Imai S, Maruyama T, Osawa M, Hattori M, Ishitani R, Nureki O, Shimada I.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1824 Pages: 1129-1129

    • DOI
      10.1016/j.bbapap.2012.06.008
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of a dominant-negative helix-loop-helix tran- scriptional regulator suggests mechanisms of autoinhibition2012

    • Author(s)
      Ishii R
    • Journal Title

      EMBO J.

      Volume: 31 Pages: 2541-2552

    • DOI
      10.1038/emboj.2012.77
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A 3D view of autotaxin2012

    • Author(s)
      Nishimasu H, Ishitani R, Aoki J, Nureki O
    • Journal Title

      Trends Pharmacol Sci.

      Volume: 33 Pages: 138-145

    • DOI
      10.1016/j.tips.2011.12.004
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the channelrhodops in 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 Pages: 369-374

    • DOI
      10.1038/nature10870
    • 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)
      Echizen Y, Tsukazaki T, Dohmae N, Ishitani R, Nureki O
    • Journal Title

      Acta Cryst.

      Volume: F67 Pages: 376-380

    • DOI
      10.1107/s1744309106007779
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function of a membrane component SecDF that enhances protein exportStructure and function of a membrane component SecDF that enhances protein export.2011

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

      Nature

      Volume: 475 Pages: 235-238

    • DOI
      10.1038/nature09980
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of autotaxin and insight into GPCR activation by lipid mediators2011

    • Author(s)
      Nishimasu H, (他), Ishitani R, Takagi J, Aoki J, Nureki O
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 18 Pages: 205-212

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for nonribosomal peptide synthesis by an aminoacyl-tRNA synthetase paralog2011

    • Author(s)
      Bonnefond L, (他), Ishitani R, Nureki O.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108 Pages: 3912-3917

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification2011

    • Author(s)
      Kato M, (他), Ishitani R, Nureki O
    • Journal Title

      Nucleic Acids Res

      Volume: (未定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C-terminal domain of archaeal O-phosphoseryl-tRNA kinase displays large-scale motion to bind the 7-bp D-stem of archaeal tRNASec2011

    • Author(s)
      Sherrer RL, (他) Ishitani R, Ho JM, Soll D, Nureki O
    • Journal Title

      Nucleic Acids Res

      Volume: (未定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for mRNA surveillance by archaeal Pelota and GTP-bound EF1α complex2010

    • Author(s)
      Kobayashi K, (他), Ishitani R, Inada T, Nureki O
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 107 Pages: 17575-17579

    • NAID
      10030494636
    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Omnipotent role of archaeal elongation factor 1 alpha (EF1α) in translational elongation and termination, and quality control of protein synthesis.2010

    • Author(s)
      Saito K, Kobayashi K, (他), Ishitani R, Nureki O, Ito K
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 107 Pages: 19242-19247

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expanding role of the Jumonji C domain as an RNA hydroxylase2010

    • Author(s)
      Noma A, Ishitani R, Kato M, Nagao A, Nureki O, Suzuki T
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 34503-7

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of an archaeal non-discriminating glutamyl-tRNA synthetase : a missing link in the evolution of Gln-tRNAGln formation2010

    • Author(s)
      Nureki O, (他), Ishitani R
    • Journal Title

      Nucleic Acids Res

      Volume: 38 Pages: 7286-7297

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms underlying the early stage of protein translocation through the Sec translocon2010

    • Author(s)
      Mori T, Ishitani R, Tsukazaki T, Nureki O, Sugita Y
    • Journal Title

      Biochemistry

      Volume: 49 Pages: 945-950

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 結晶構造解析と分子動力学シミュレーションから調べるタンパク質のダイナミクス2012

    • Author(s)
      石谷隆一郎
    • Organizer
      JSIAM2012
    • Place of Presentation
      稚内
    • Year and Date
      2012-08-30
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] Structural basis for mRNA surveillance by archaeal Pelota and GTP-bound EF1α complex2012

    • Author(s)
      石谷隆一郎
    • Organizer
      XXIV tRNA Conference
    • Place of Presentation
      Olmue, Chile
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] Structural basis forH+-coupled symport mechanism by POT2012

    • Author(s)
      石谷隆一郎
    • Organizer
      GRCon Membrane Transport Proteins
    • Place of Presentation
      Les Diablerets Conference Center, Les Diablerets, Switzerland
    • Related Report
      2012 Final Research Report
  • [Presentation] Structural basis for H+-coupled symport mechanism by POT2012

    • Author(s)
      石谷隆一郎
    • Organizer
      GRC on Membrane Transport Proteins
    • Place of Presentation
      Les Diablerets Conference Center, Les Diablerets, Switzerland
    • Related Report
      2012 Annual Research Report
  • [Presentation] Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition2011

    • Author(s)
      石谷隆一郎
    • Organizer
      分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(招待講演)
    • Year and Date
      2011-12-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 古細菌由来Pelota・EF1α・GTP複合体によるmRNA品質管理機構の構造基盤2010

    • Author(s)
      石谷隆一郎
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Book] 酵素利用技術大系-基礎・解析から改変・高機能化・産業利用まで-(1章1節2)2010

    • Author(s)
      石谷隆一郎、荒磯裕平、野澤佳世
    • Total Pages
      800
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL
      http://www.nurekilab.net/
    • Related Report
      2012 Final Research Report
  • [Remarks] 濡木研究室

    • URL
      http://www.nurekilab.net/
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL
      http://www.nurekilab.net/
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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