Structure determination of human membrane transporters

• Project/Area Number: 25650023
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Kyoto University
• Principal Investigator: SHIMAMURA Tatsuro 京都大学, 医学(系)研究科(研究院), 講師 (90391979)
• Co-Investigator(Kenkyū-buntansha): NOMURA Morimichi 京都大学, 大学院医学研究科, 助教 (10314246)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Yoshiki 京都大学, 大学院医学研究科, 研究員 (10632333) ; OGASAWARA Satoshi 京都大学, 大学院医学研究科, 研究員 (30546685) ; ARAKAWA Takatoshi 京都大学, 大学院医学研究科, 研究員 (30523766)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膜輸送体 / 結晶構造解析 / 創薬 / 輸送体 / トランスポーター / X線結晶構造解析

Outline of Final Research Achievements

Membrane transporters are drug targets because they are important causes of diseases. Therefore, the structural information of human membrane transporters is very useful for the rational design of new drugs. However, it is difficult to determine the crystal structure of membrane transporters because of their instabilities. We tried to crystallize mammalian transporters using the recently developed methods for the membrane protein crystallization and succeeded to crystallize some of the membrane transporters.

Research Products

• [Journal Article] Grease matrix as a versatile carrier of proteins for serial crystallography. (2015)
  • Author(s): Sugahara M, Shimamura T, et al.
  • Journal Title: Nat Methods. Volume: 12 Issue: 1 Pages: 61-63
  • DOI: 10.1038/nmeth.3172
  • NAID: 120005682565
  • Peer Reviewed
• [Journal Article] Diverse application platform for hard X-ray diffraction in SACLA (DAPHNIS): application to serial protein crystallography using an X-ray free-electron laser. (2015)
  • Author(s): Tono K, Shimamura T, et al.
  • Journal Title: J. Synchrotron Rad. Volume: 22 Issue: 3 Pages: 532-537
  • DOI: 10.1107/s1600577515004464
  • Peer Reviewed
• [Journal Article] Proteoliposome-based selection of a recombinant antibody fragment against the human M2 muscarinic acetylcholine receptor. (2014)
  • Author(s): Suharni, Nomura Y, Arakawa T, Hino T, Abe H, Nakada-Nakura Y, Sato Y, Iwanari H, Shiroishi M, Asada H, Shimamura T, Murata T, Kobayashi T, Hamakubo T, Iwata S, Nomura N.
  • Journal Title: Monoclon Antib Immunodiagn Immunother Volume: 33 Issue: 6 Pages: 378-385
  • DOI: 10.1089/mab.2014.0041
  • NAID: 120005530933
  • Peer Reviewed
• [Journal Article] Crystal structure of a symmetric football-shaped GroEL:GroES2-ATP14 complex determined at 3.8Å reveals rearrangement between two GroEL rings. (2014)
  • Author(s): Koike-Takeshita A, Arakawa T, Taguchi H, Shimamura T.
  • Journal Title: J Mol Biol. Volume: 426 Issue: 21 Pages: 3634-41
  • DOI: 10.1016/j.jmb.2014.08.017
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] X-ray structure of histamine H1 receptor (2014)
  • Author(s): Shimamura T.
  • Journal Title: Nihon Yakurigaku Zasshi. Volume: 144 Pages: 43-4
  • NAID: 130004437205
• [Journal Article] ヒスタミンH1受容体 (2014)
  • Author(s): 島村達郎
  • Journal Title: 日本薬理学会誌 Volume: 未定
  • Peer Reviewed
• [Journal Article] ヒスタミン受容体 (2013)
  • Author(s): 島村達郎
  • Journal Title: 膜タンパク質構造研究 Volume: １ Pages: 11-18
  • Peer Reviewed
• [Presentation] ヒスタミンH1受容体の構造解析とin silico screening (2014)
  • Author(s): 島村達郎
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 博多
  • Year and Date: 2014-04-25
  • Invited
• [Presentation] ヒスタミンH1受容体の構造解析とin silico screening (2014)
  • Author(s): 島村達郎
  • Organizer: 第８７回日本内分泌学会学術総会
  • Place of Presentation: 博多
• [Presentation] Crystal structure of Histamine H1 receptor and drug design. (2013)
  • Author(s): Shimamura T
  • Organizer: The 11th International Symposium for Future Drug Discovery and Medical Care.
  • Place of Presentation: Sapporo
  • Invited