Structural biology of secondary active transporters

2012 Fiscal Year Final Research Report

• Project/Area Number: 22687007
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: The 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
• Keywords: X 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

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.

Research Products

• [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)
  • 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)
  • 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)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Presentation] Structural basis for mRNA surveillance by archaeal Pelota and GTP-bound EF1α complex (2012)
  • Author(s): 石谷隆一郎
  • Organizer: XXIV tRNA Conference
  • Place of Presentation: Olmue, Chile
  • Year and Date: 20121202-1206
• [Presentation] Structural basis forH+-coupled symport mechanism by POT (2012)
  • Author(s): 石谷隆一郎
  • Organizer: GRCon Membrane Transport Proteins
  • Place of Presentation: Les Diablerets Conference Center, Les Diablerets, Switzerland
  • Year and Date: 20120701-07 06
• [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
• [Remarks]
  • URL: http://www.nurekilab.net/