Establishing key technologies for structure-based design of medium-sized therapeutic molecules targeting human membrane proteins

• Project/Area Number: 19H00923
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Kyoto University
• Principal Investigator: Iwata So 京都大学, 医学研究科, 教授 (60452330)
• Co-Investigator(Kenkyū-buntansha): 野村 紀通 京都大学, 医学研究科, 准教授 (10314246)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000); Fiscal Year 2023: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2022: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2021: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2020: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2019: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 膜タンパク質 / 創薬ターゲット / クライオ電子顕微鏡単粒子解析 / 中分子医薬品 / 抗ウイルス薬 / B型肝炎ウイルス / 抗体 / 中分子ペプチド / ウイルス感染受容体 / 中分子 / クライオ電子顕微鏡 / 創薬 / ファージディスプレイ / X線結晶構造解析 / 構造生物学

Outline of Research at the Start

がん、高血圧、慢性炎症といった疾病に対する医薬品の開発には大きな社会的要請がある。市販の医薬品の50%以上がGタンパク質共役受容体 (GPCR)、膜輸送体、あるいは膜内在性酵素を作用点としており、膜タンパク質は創薬において重要なターゲットである。低分子医薬や抗体医薬のもつ問題点を解消するため、本研究ではヒト膜タンパク質の機能や相互作用を制御する中分子医薬リードの創出とその薬理作用機序の構造学的検証を行う。

Outline of Final Research Achievements

Medium-sized molecules are a promising drug discovery modality for intervening in membrane protein-membrane protein interactions that consist of flat and broad binding interfaces. In this study, we conducted basic research towards structure-based design of medium-sized therapeutic drugs, using the interaction between the hepatitis B virus protein and the human hepatocyte membrane receptor as a model target. The apo structure of the hepatitis B virus entry receptor NTCP was determined by cryo-electron microscopy single particle analysis. Furthermore, the structure of the NTCP-HBV envelope preS1 domain (lipopeptide) complex was determined. The virus-host receptor binding was successfully visualized at high resolution. These findings are an important foundation that opens new avenues for the development of anti-HBV drugs in the medium-sized molecular modality based on structural information.

Academic Significance and Societal Importance of the Research Achievements

C型肝炎がほぼ克服された一方で、B型肝炎ウイルス (HBV) の感染を原因としたB型肝炎は依然として公衆衛生上の主要な問題である。慢性B型肝炎は肝硬変や肝細胞がんを引き起こし、全世界で年間90万人が死亡している。また、国内では近年 genotype A（欧米型）のHBV感染による急性B型肝炎が大都市部で急速に増加している。簡便に投与可能なHBV感染抑制薬を開発することにより肝炎罹患の根本原因に歯止めをかけることが強く望まれている。本研究は、HBVと感染受容体NTCP間の高親和性相互作用形成の機序を明らかにし、HBV感染抑制作用のある中分子医薬開発を大きく前進させるための重要な基盤を構築した。

Research Products

• [Int'l Joint Research] Stockholm University(スウェーデン)
• [Int'l Joint Research] Stockholm University(スウェーデン)
• [Int'l Joint Research] University of California, San Francisco(米国)
• [Int'l Joint Research] Fudan University(中国)
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  • Author(s): Li Hongjie、Nakajima Yoshiki、Nango Eriko、Owada Shigeki、Yamada Daichi、Tosha Takehiko、Tono Kensuke、Joti Yasumasa、Hatsui Takaki、Yabashi Makina、Kubo Minoru、Iwata So、Isobe Hiroshi、Yamaguchi Kizashi、Suga Michihiro、Shen Jian-Ren
  • Journal Title: Nature Volume: 626 Issue: 7999 Pages: 670-677
  • DOI: 10.1038/s41586-023-06987-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural basis of hepatitis B virus receptor binding (2024)
  • Author(s): Asami Jinta、Park Jae-Hyun、Nomura Yayoi、Kobayashi Chisa、Mifune Junki、Ishimoto Naito、Uemura Tomoko、Liu Kehong、Sato Yumi、Zhang Zhikuan、Muramatsu Masamichi、Wakita Takaji、Drew David、Iwata So、Shimizu Toshiyuki、Watashi Koichi、Park Sam-Yong、Nomura Norimichi、Ohto Umeharu
  • Journal Title: Nature Structural & Molecular Biology Volume: 31 Issue: 3 Pages: 447-454
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• [Journal Article] Interaction modes of human orexin 2 receptor with selective and nonselective antagonists studied by NMR spectroscopy (2024)
  • Author(s): Imamura Kayo、Akagi Ken-Ichi、Miyanoiri Yohei、Tsujimoto Hirokazu、Hirokawa Takatsugu、Ashida Hideo、Murakami Kaori、Inoue Asuka、Suno Ryoji、Ikegami Takahisa、Sekiyama Naotaka、Iwata So、Kobayashi Takuya、Tochio Hidehito
  • Journal Title: Structure Volume: 32 Issue: 3 Pages: 352-361
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  • Peer Reviewed / Open Access
• [Journal Article] Crystal structure reveals the binding mode and selectivity of a photoswitchable ligand for the adenosine A2A receptor (2024)
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• [Journal Article] Time-resolved serial crystallography to track the dynamics of carbon monoxide in the active site of cytochrome c oxidase (2023)
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• [Journal Article] Visualizing the DNA repair process by a photolyase at atomic resolution (2023)
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• [Journal Article] Structural insights into the agonists binding and receptor selectivity of human histamine H4 receptor (2023)
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  • Journal Title: Nature Communications Volume: 14 Issue: 1 Pages: 6538-6538
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• [Journal Article] A versatile approach to high-density microcrystals in lipidic cubic phase for room-temperature serial crystallography (2023)
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  • Journal Title: Journal of Applied Crystallography Volume: 56 Issue: 5 Pages: 1361-1370
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mapping protein dynamics at high spatial resolution with temperature-jump X-ray crystallography (2023)
  • Author(s): Wolff, A. M., Nango, E., Young, I. D., Brewster, A. S., Kubo, M., Nomura, T., Sugahara, M., Owada, S., Barad, B. A., Ito, K., Bhowmick, A., Carbajo, S., Hino, T., Holton, J. M., Im, D., O'Riordan, L. J., Tanaka, T., Tanaka, R., Sierra, R. G., Yumoto, F., Tono, K., Iwata, S., et al
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• [Journal Article] Optical control of ultrafast structural dynamics in a fluorescent protein (2023)
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• [Journal Article] Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus (2023)
  • Author(s): Bui Han Ba、Watanabe Satoshi、Nomura Norimichi、Liu Kehong、Uemura Tomoko、Inoue Michio、Tsutsumi Akihisa、Fujita Hiroyuki、Kinoshita Kengo、Kato Yukinari、Iwata So、Kikkawa Masahide、Inaba Kenji
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• [Journal Article] Serial Femtosecond Crystallography Reveals that Photoactivation in a Fluorescent Protein Proceeds via the Hula Twist Mechanism (2023)
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• [Journal Article] Structural insight into an anti-BRIL Fab as a G-protein-coupled receptor crystallization chaperone (2023)
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  • Peer Reviewed
• [Journal Article] Structure and mechanism of oxalate transporter OxlT in an oxalate-degrading bacterium in the gut microbiota (2023)
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  • Peer Reviewed
• [Journal Article] Ultrafast structural changes direct the first molecular events of vision (2023)
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• [Journal Article] <i>In vitro</i>pharmacological profile of KW-6356, a novel adenosine A_2Areceptor antagonist/inverse agonist (2023)
  • Author(s): Ohno Yutaro、Suzuki Michihiko、Asada Hidetsugu、Kanda Tomoyuki、Saki Mayumi、Miyagi Hikaru、Yasunaga Mai、Suno Chiyo、Iwata So、Saito Jun-ichi、Uchida Shinichi
  • Journal Title: Molecular Pharmacology Volume: 未定 Issue: 6 Pages: 311-324
  • DOI: 10.1124/molpharm.122.000633
  • Peer Reviewed
• [Journal Article] B型肝炎ウイルスの感染受容体NTCPの構造 (2023)
  • Author(s): 野村紀通
  • Journal Title: 医学のあゆみ Volume: 285 Pages: 1082-71083
• [Journal Article] Recent progress in membrane protein dynamics revealed by X-ray free electron lasers: Molecular movies of microbial rhodopsins (2023)
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  • DOI: 10.1016/j.sbi.2023.102629
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ドパミン受容体を標的とした統合失調症治療薬─構造生物学からの洞察 (2023)
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  • Journal Title: 医学のあゆみ Volume: 286 Pages: 537-543
• [Journal Article] Serial crystallography captures dynamic control of sequential electron and proton transfer events in a flavoenzyme (2022)
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• [Journal Article] Structural insights into the HBV receptor and bile acid transporter NTCP (2022)
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structure of the?bile acid transporter?and HBV receptor NTCP (2022)
  • Author(s): Asami Jinta、Kimura Kanako Terakado、Fujita-Fujiharu Yoko、Ishida Hanako、Zhang Zhikuan、Nomura Yayoi、Liu Kehong、Uemura Tomoko、Sato Yumi、Ono Masatsugu、Yamamoto Masaki、Noda Takeshi、Shigematsu Hideki、Drew David、Iwata So、Shimizu Toshiyuki、Nomura Norimichi、Ohto Umeharu
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• [Journal Article] Excited-state intermediates in a designer protein encoding a phototrigger caught by an X-ray free-electron laser (2022)
  • Author(s): Liu X.、Liu P.、Li H.、Xu Z.、Jia L.、Xia Y.、Yu M.、Tang W.、Zhu X.、Chen C.、Zhang Y.、Nango E.、Tanaka R.、Luo F.、Kato K.、Nakajima Y.、Kishi S.、Yu H.、Matsubara N.、Owada S.、Tono K.、Iwata S.、Yu L.-J.、Shen J.-R.、Wang J.
  • Journal Title: Nature Chemistry Volume: 14 Issue: 9 Pages: 1054-1060
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• [Journal Article] Structure of SARS-CoV-2 membrane protein essential for virus assembly (2022)
  • Author(s): Zhang Zhikuan、Nomura Norimichi、Muramoto Yukiko、Ekimoto Toru、Uemura Tomoko、Liu Kehong、Yui Moeko、Kono Nozomu、Aoki Junken、Ikeguchi Mitsunori、Noda Takeshi、Iwata So、Ohto Umeharu、Shimizu Toshiyuki
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 4399-4399
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• [Journal Article] Structural insights into the G protein selectivity revealed by the human EP3-Gi signaling complex (2022)
  • Author(s): Ryoji Suno, Yukihiko Sugita, Kazushi Morimoto, Hiroko Takazaki, Hirokazu Tsujimoto, Mika Hirose, Chiyo Suno-Ikeda, Norimichi Nomura, Tomoya Hino, Asuka Inoue, Kenji Iwasaki, Takayuki Kato, So Iwata, Takuya Kobayashi
  • Journal Title: Cell Rep. Volume: 40(11) Issue: 11 Pages: 111323-111323
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• [Journal Article] Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice. (2022)
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• [Journal Article] Molecular basis for anti-insomnia drug design from structure of lemborexant-bound orexin 2 receptor (2022)
  • Author(s): Asada Hidetsugu、Im Dohyun、Hotta Yunhon、Yasuda Satoshi、Murata Takeshi、Suno Ryoji、Iwata So
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• [Journal Article] Serial femtosecond X-ray crystallography of an anaerobically formed catalytic intermediate of copper amine oxidase (2022)
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• [Journal Article] Conformational alterations in unidirectional ion transport of a light-driven chloride pump revealed using X-ray free electron lasers. (2022)
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• [Journal Article] Structure, mechanism and lipid-mediated remodeling of the mammalian Na+/H+ exchanger NHA2 (2022)
  • Author(s): Matsuoka Rei、Fudim Roman、Jung Sukkyeong、Zhang Chenou、Bazzone Andre、Chatzikyriakidou Yurie、Robinson Carol V.、Nomura Norimichi、Iwata So、Landreh Michael、Orellana Laura、Beckstein Oliver、Drew David
  • Journal Title: Nature Structural and Molecular Biology Volume: 29 Issue: 2 Pages: 108-120
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• [Journal Article] Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine. (2022)
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• [Journal Article] Crystal structure of CmABCB1 multi-drug exporter in lipidic mesophase revealed by LCP-SFX (2021)
  • Author(s): Pan Dongqing、Oyama Ryo、Sato Tomomi、Nakane Takanori、Mizunuma Ryo、Matsuoka Keita、Joti Yasumasa、Tono Kensuke、Nango Eriko、Iwata So、Nakatsu Toru、Kato Hiroaki
  • Journal Title: IUCrJ Volume: 9 Issue: 1 Pages: 134-145
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• [Journal Article] Vibrational spectroscopy analysis of ligand efficacy in human M2 muscarinic acetylcholine receptor (M2R) (2021)
  • Author(s): Katayama Kota、Suzuki Kohei、Suno Ryoji、Kise Ryoji、Tsujimoto Hirokazu、Iwata So、Inoue Asuka、Kobayashi Takuya、Kandori Hideki
  • Journal Title: Communications Biology Volume: 4 Issue: 1 Pages: 1-10
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  • Peer Reviewed / Open Access
• [Journal Article] Microcrystal preparation for serial femtosecond X-ray crystallography of bacterial copper amine oxidase (2021)
  • Author(s): Murakawa Takeshi、Suzuki Mamoru、Arima Toshi、Sugahara Michihiro、Tanaka Tomoyuki、Tanaka Rie、Iwata So、Nango Eriko、Tono Kensuke、Hayashi Hideyuki、Fukui Kenji、Yano Takato、Tanizawa Katsuyuki、Okajima Toshihide
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  • Peer Reviewed
• [Journal Article] Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides (2021)
  • Author(s): Ghilarov Dmitry、Inaba-Inoue Satomi、Stepien Piotr、Qu Feng、Michalczyk Elizabeth、Pakosz Zuzanna、Nomura Norimichi、Ogasawara Satoshi、Walker Graham Charles、Rebuffat Sylvie、Iwata So、Heddle Jonathan Gardiner、Beis Konstantinos
  • Journal Title: Science Advances Volume: 7 Issue: 37
  • DOI: 10.1126/sciadv.abj5363
  • NAID: 120007147067
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The structural basis of bacterial manganese import (2021)
  • Author(s): Neville Stephanie L.、Sj?hamn Jennie、Watts Jacinta A.、MacDermott-Opeskin Hugo、Fairweather Stephen J.、Ganio Katherine、Carey Hulyer Alex、McGrath Aaron P.、Hayes Andrew J.、Malcolm Tess R.、Davies Mark R.、Nomura Norimichi、Iwata So、O’Mara Megan L.、Maher Megan J.、McDevitt Christopher A.
  • Journal Title: Science Advances Volume: 7 Issue: 32
  • DOI: 10.1126/sciadv.abg3980
  • NAID: 120007149018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The three-dimensional structure of <i>Drosophila melanogaster</i> (6?4) photolyase at room temperature (2021)
  • Author(s): Cellini Andrea、Yuan Wahlgren Weixiao、Henry L?ocadie、Pandey Suraj、Ghosh Swagatha、Castillon Leticia、Claesson Elin、Takala Heikki、K?bel Joachim、Nimmrich Amke、Kuznetsova Valentyna、Nango Eriko、Iwata So、Owada Shigeki、Stojkovi? Emina A.、Schmidt Marius、Ihalainen Janne A.、Westenhoff Sebastian
  • Journal Title: Acta Crystallographica Section D Structural Biology Volume: 77 Issue: 8 Pages: 1001-1009
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• [Journal Article] Cryo-EM structure of the human MT1-Gi signaling complex. (2021)
  • Author(s): Okamoto, H. H., Miyauchi, H., Inoue, A., Raimondi, F., Tsujimoto, H., Kusakizako, T., Shihoya, W., Yamashita, K., Suno, R., Nomura, N., Kobayashi, T., Iwata, S., Nishizawa, T. and Nureki, O.
  • Journal Title: Nat. Struct. Mol. Biol. Volume: 28 Issue: 8 Pages: 694-701
  • DOI: 10.1038/s41594-021-00634-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Endogenous agonist?bound S1PR3 structure reveals determinants of G protein?subtype bias (2021)
  • Author(s): Maeda Shintaro、Shiimura Yuki、Asada Hidetsugu、Hirata Kunio、Luo Fangjia、Nango Eriko、Tanaka Nobuo、Toyomoto Masayasu、Inoue Asuka、Aoki Junken、Iwata So、Hagiwara Masatoshi
  • Journal Title: Science Advances Volume: 7 Issue: 24
  • DOI: 10.1126/sciadv.abf5325
  • NAID: 120007052733
  • Peer Reviewed / Open Access
• [Journal Article] The structure of MgtE in the absence of magnesium provides new insights into channel gating. (2021)
  • Author(s): Jin F, Sun M, Fujii T, Yamada Y, Wang J, Maturana AD, Wada M, Su S, Ma J, Takeda H, Kusakizako T, Tomita A, Nakada-Nakura Y, Liu K, Uemura T, Nomura Y, Nomura N, Ito K, Nureki O, Namba K, Iwata S, Yu Y, Hattori M.
  • Journal Title: PLoS Biology Volume: 19 Issue: 4 Pages: e3001231-e3001231
  • DOI: 10.1371/journal.pbio.3001231
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Capturing structural changes of the S1 to S2 transition of photosystem II using time-resolved serial femtosecond crystallography (2021)
  • Author(s): H Li, Y Nakajima, T Nomura, M Sugahara, S Yonekura, SK Chan, T Nakane, T Yamane, Y Umena, M Suzuki, T Masuda, T Motomura, H Naitow, Y Matsuura, T Kimura, K Tono, S Owada, Y Joti, R Tanaka, E Nango, F Akita, M Kubo, S Iwata, JR Shen and M Suga
  • Journal Title: IUCrJ Volume: 8 Issue: 3 Pages: 431-443
  • DOI: 10.1107/s2052252521002177
  • NAID: 120007037379
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein. (2021)
  • Author(s): Nojima S, Fujita Y, Kimura KT, Nomura N, Suno R, Morimoto K, Yamamoto M, Noda T, Iwata S, Shigematsu H, Kobayashi T.
  • Journal Title: Structure Volume: 29 Issue: 3 Pages: 252-260
  • DOI: 10.1016/j.str.2020.11.007
  • Peer Reviewed / Open Access
• [Journal Article] S1PR3?G12-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation (2021)
  • Author(s): Toyomoto Masayasu、Inoue Asuka、Iida Kei、Denawa Masatsugu、Kii Isao、Ngako Kadji Francois Marie、Kishi Takayuki、Im Dohyun、Shimamura Tatsuro、Onogi Hiroshi、Yoshida Suguru、Iwata So、Aoki Junken、Hosoya Takamitsu、Hagiwara Masatoshi
  • Journal Title: Cell Chemical Biology Volume: 未定 Issue: 8 Pages: 1132-1144
  • DOI: 10.1016/j.chembiol.2021.01.004
  • Peer Reviewed / Open Access
• [Journal Article] High-resolution crystal structures of transient intermediates in the phytochrome photocycle (2021)
  • Author(s): Carrillo Melissa et al.
  • Journal Title: Structure Volume: 未定 Issue: 7 Pages: 743-754
  • DOI: 10.1016/j.str.2021.03.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin (2021)
  • Author(s): Oda Kazumasa、Nomura Takashi、Nakane Takanori、Yamashita Keitaro、Inoue Keiichi、Ito Shota、Vierock Johannes、Hirata Kunio、Maturana Andres D、Katayama Kota、( 32 authers )、Kandori Hideki、Hegemann Peter、Iwata So、Kubo Minoru、Nishizawa Tomohiro、Nureki Osamu
  • Journal Title: eLife Volume: 10 Pages: 1-21
  • DOI: 10.7554/elife.62389
  • NAID: 120006996980
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias (2021)
  • Author(s): Maeda S, Shiimura Y, Asada H, Hirata K, Luo F, Nango E, Tanaka N, Toyomoto M, Inoue A, Aoki J, *Iwata S and *Hagiwara M.
  • Journal Title: Science Advances Volume: 未定
  • NAID: 120007052733
  • Peer Reviewed / Open Access
• [Journal Article] Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals (2020)
  • Author(s): Wolff, A. M., Kubo, M. et al.
  • Journal Title: IUCrJ Volume: 7 Issue: 2 Pages: 306-323
  • DOI: 10.1107/s205225252000072x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser (2020)
  • Author(s): Claesson Elin、et al.
  • Journal Title: eLife Volume: 9
  • DOI: 10.7554/elife.53514
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural insights into tetraspanin CD9 function (2020)
  • Author(s): Umeda Rie、Satouh Yuhkoh、Takemoto Mizuki、Nakada-Nakura Yoshiko、Liu Kehong、Yokoyama Takeshi、Shirouzu Mikako、Iwata So、Nomura Norimichi、Sato Ken、Ikawa Masahito、Nishizawa Tomohiro、Nureki Osamu
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 643-651
  • DOI: 10.1038/s41467-020-15459-7
  • NAID: 120006957458
  • Peer Reviewed / Open Access
• [Journal Article] The discovery of a new antibody for BRIL-fused GPCR structure determination (2020)
  • Author(s): Miyagi Hikaru、Asada Hidetsugu、Suzuki Michihiko、Takahashi Yuichi、Yasunaga Mai、Suno Chiyo、Iwata So、Saito Jun-ichi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 11669-11669
  • DOI: 10.1038/s41598-020-68355-x
  • Peer Reviewed / Open Access
• [Journal Article] Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode (2020)
  • Author(s): Shiimura Yuki、Horita Shoichiro、Hamamoto Akie、Asada Hidetsugu、Hirata Kunio、Tanaka Misuzu、Mori Kenji、Uemura Tomoko、Kobayashi Takuya、Iwata So、Kojima Masayasu
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41467-020-17554-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion (2020)
  • Author(s): Matoba Kazuaki、Kotani Tetsuya、Tsutsumi Akihisa、Tsuji Takuma、Mori Takaharu、Noshiro Daisuke、Sugita Yuji、Nomura Norimichi、Iwata So、Ohsumi Yoshinori、Fujimoto Toyoshi、Nakatogawa Hitoshi、Kikkawa Masahide、Noda Nobuo N.
  • Journal Title: Nature Structural & Molecular Biology Volume: 27 Issue: 12 Pages: 1185-1193
  • DOI: 10.1038/s41594-020-00518-w
  • Peer Reviewed / Open Access
• [Journal Article] Isoprenoid-chained lipid EROCOC17+4: a new matrix for membrane protein crystallization and a crystal delivery medium in serial femtosecond crystallography (2020)
  • Author(s): Ihara Kentaro、Hato Masakatsu、Nakane Takanori、Yamashita Keitaro、Kimura-Someya Tomomi、Hosaka Toshiaki、Ishizuka-Katsura Yoshiko、Tanaka Rie、Tanaka Tomoyuki、Sugahara Michihiro、Hirata Kunio、Yamamoto Masaki、Nureki Osamu、Tono Kensuke、Nango Eriko、Iwata So、Shirouzu Mikako
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 19305-19305
  • DOI: 10.1038/s41598-020-76277-x
  • Peer Reviewed / Open Access
• [Journal Article] Isolation and thermal stabilization of mouse ferroportin (2020)
  • Author(s): Deshpande Chandrika N.、Azucenas Corbin R.、Qiao Bo、Nomura Norimichi、Xin Vicky、Font Josep、Iwata So、Ganz Tomas、Nemeth Elizabeta、Mackenzie Bryan、Jormakka Mika
  • Journal Title: FEBS Open Bio Volume: 11 Issue: 1 Pages: 26-34
  • DOI: 10.1002/2211-5463.13039
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone (2020)
  • Author(s): Im Dohyun、Inoue Asuka、Fujiwara Takaaki、Nakane Takanori、Yamanaka Yasuaki、Uemura Tomoko、Mori Chihiro、Shiimura Yuki、Kimura Kanako Terakado、Asada Hidetsugu、Nomura Norimichi、Tanaka Tomoyuki、Yamashita Ayumi、Nango Eriko、Tono Kensuke、Kadji Francois Marie Ngako、Aoki Junken、Iwata So、Shimamura Tatsuro
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-11
  • DOI: 10.1038/s41467-020-20221-0
  • NAID: 120006943309
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone (2020)
  • Author(s): Asada Hidetsugu、Inoue Asuka、Ngako Kadji Francois Marie、Hirata Kunio、Shiimura Yuki、Im Dohyun、Shimamura Tatsuro、Nomura Norimichi、Iwanari Hiroko、Hamakubo Takao、Kusano-Arai Osamu、Hisano Hiromi、Uemura Tomoko、Suno Chiyo、Aoki Junken、Iwata So
  • Journal Title: Structure Volume: 28 Issue: 4 Pages: 418-425.e4
  • DOI: 10.1016/j.str.2019.12.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Toward G protein-coupled receptor structure-based drug design using X-ray lasers (2019)
  • Author(s): Ishchenko Andrii、Stauch Benjamin、Han Gye Won、Batyuk Alexander、Shiriaeva Anna、Li Chufeng、Zatsepin Nadia、Weierstall Uwe、Liu Wei、Nango Eriko、Nakane Takanori、Tanaka Rie、Tono Kensuke、Joti Yasumasa、Iwata So、Moraes Isabel、Gati Cornelius、Cherezov Vadim
  • Journal Title: IUCrJ Volume: 6 Issue: 6 Pages: 1106-1119
  • DOI: 10.1107/s2052252519013137
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ligand Binding-Induced Structural Changes in the M2 Muscarinic Acetylcholine Receptor Revealed by Vibrational Spectroscopy. (2019)
  • Author(s): K.Katayama, K. Suzuki, R. Suno, H. Tsujimoto, S. Iwata, T. Kobayashi, H. Kandori*
  • Journal Title: J Phys Chem Lett. Volume: 10(22) Issue: 22 Pages: 7270-7276
  • DOI: 10.1021/acs.jpclett.9b02942
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High-viscosity sample-injection device for serial femtosecond crystallography at atmospheric pressure (2019)
  • Author(s): Shimazu Yoshiaki、Tono Kensuke、Tanaka Tomoyuki、Yamanaka Yasuaki、Nakane Takanori、Mori Chihiro、Terakado Kimura Kanako、Fujiwara Takaaki、Sugahara Michihiro、Tanaka Rie、Doak R. Bruce、Shimamura Tatsuro、Iwata So、Nango Eriko、Yabashi Makina
  • Journal Title: Journal of Applied Crystallography Volume: 52 Issue: 6 Pages: 1280-1288
  • DOI: 10.1107/s1600576719012846
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improvement of Production and Isolation of Human Neuraminidase-1 in Cellulo Crystals (2019)
  • Author(s): Koiwai Kotaro et al.
  • Journal Title: ACS Applied Bio Materials Volume: 2 Issue: 11 Pages: 4941-4952
  • DOI: 10.1021/acsabm.9b00686
  • Peer Reviewed / Open Access
• [Journal Article] High-resolution crystal structures of a myxobacterial phytochrome at cryo and room temperatures (2019)
  • Author(s): Sanchez Juan C.et al.
  • Journal Title: Structural Dynamics Volume: 6 Issue: 5 Pages: 054701-054701
  • DOI: 10.1063/1.5120527
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] FRET-assisted photoactivation of flavoproteins for in vivo two-photon optogenetics (2019)
  • Author(s): Kinjo Tomoaki、Terai Kenta、Horita Shoichiro、Nomura Norimichi、Sumiyama Kenta、Togashi Kaori、Iwata So、Matsuda Michiyuki
  • Journal Title: Nature Methods Volume: 16 Issue: 10 Pages: 1029-1036
  • DOI: 10.1038/s41592-019-0541-5
  • Peer Reviewed / Open Access
• [Journal Article] Bacteriorhodopsin: Structural Insights Revealed Using X-Ray Lasers and Synchrotron Radiation (2019)
  • Author(s): Wickstrand Cecilia、Nogly Przemyslaw、Nango Eriko、Iwata So、Standfuss J?rg、Neutze Richard
  • Journal Title: Annual Review of Biochemistry Volume: 88 Issue: 1 Pages: 59-83
  • DOI: 10.1146/annurev-biochem-013118-111327
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structures of the 5-HT2A receptor in complex with the antipsychotics risperidone and zotepine (2019)
  • Author(s): Kimura Kanako Terakado、Asada Hidetsugu、Inoue Asuka、Kadji Francois Marie Ngako、Im Dohyun、Mori Chihiro、Arakawa Takatoshi、Hirata Kunio、Nomura Yayoi、Nomura Norimichi、Aoki Junken、Iwata So、Shimamura Tatsuro
  • Journal Title: Nature Structural & Molecular Biology Volume: 26 Issue: 2 Pages: 121-128
  • DOI: 10.1038/s41594-018-0180-z
  • Peer Reviewed
• [Journal Article] Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interface (2019)
  • Author(s): Toyoda Y, Morimoto K, Suno R, et al.
  • Journal Title: Nature Chemical Biology Volume: 15 Issue: 1 Pages: 18-26
  • DOI: 10.1038/s41589-018-0131-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Crystal structure of the endogenous agonist-bound prostanoid receptor EP3. (2019)
  • Author(s): Morimoto K, Suno R, Hotta Y, Yamashita K, Hirata K, Yamamoto M, Narumiya S, Iwata S, Kobayashi T.
  • Journal Title: Nat Chem Biol. Volume: 15(1) Issue: 1 Pages: 8-10
  • DOI: 10.1038/s41589-018-0171-8
  • Peer Reviewed / Open Access
• [Presentation] 拠点の紹介：構造解析ユニット (2023)
  • Author(s): 岩田想
  • Organizer: 京都大学BINDS合同シンポジウム：オープンイノベーションから創薬へ 2023
  • Invited
• [Presentation] 抗体を用いた膜タンパク質構造研究 (2023)
  • Author(s): 野村紀通
  • Organizer: 京都大学BINDS合同シンポジウム：オープンイノベーションから創薬へ 2023
  • Invited
• [Presentation] X線結晶構造解析で見るTNF阻害剤の分子機構 (2023)
  • Author(s): 野村紀通
  • Organizer: 潰瘍性大腸炎Webセミナー「TNFα阻害剤をMOAから再考する」
  • Invited
• [Presentation] 胆汁酸トランスポーターNTCPによるB型肝炎ウイルス認識の構造基盤 (2023)
  • Author(s): 浅見仁太*、朴在鉉、野村弥生、石本直偉士*、小林ちさ*、御舩淳紀、植村智子、劉紅、佐藤有美、村松正道、脇田隆字、Drew David、渡士幸一、岩田想、清水敏之、朴三用、野村紀通、大戸梅治
  • Organizer: 日本薬学会第143年会
• [Presentation] 高速分子動画：これまでの成果と今後の展開 (2022)
  • Author(s): 岩田想
  • Organizer: 第95回日本生化学会大会
  • Invited
• [Presentation] Unveiling membrane protein structures with the aid of antibody toolkits (2022)
  • Author(s): Norimichi Nomura
  • Organizer: OIST-Kyoto University Joint Workshop -Challenges in Biomedical Complexity-
  • Invited
• [Presentation] 膜タンパク質構造研究 この10年 (2022)
  • Author(s): 野村紀通
  • Organizer: 京都大学大学院医学研究科 医学研究支援センター開設10周年記念セミナー
  • Invited
• [Presentation] Measurement systems for biomolecular movies using X-ray free electron lasers (2022)
  • Author(s): 岩田想
  • Organizer: SACLA Users’ Meeting 2022
• [Presentation] 抗体フラグメントを用いた創薬ターゲット膜タンパク質構造研究 (2022)
  • Author(s): 岩田想
  • Organizer: 第25回アディポサイエンス・シンポジウム
  • Invited
• [Presentation] 高速分子動画による構造ダイナミクス研究 (2022)
  • Author(s): 岩田想
  • Organizer: 第35回日本放射光学会年会・放射光科学合同シンポジウム
  • Invited
• [Presentation] B型肝炎ウイルス受容体NTCPの構造解析 (2022)
  • Author(s): 浅見仁太、木村香菜子、藤田陽子、石田英子、張志寛、野村弥生、劉紅、植村智子、佐藤有美、小野真嗣、山本雅貴、野田岳志、重松秀樹、Drew David、岩田想、清水敏之、野村紀通、大戸梅治
  • Organizer: 日本薬学会第142年会
• [Presentation] Molecular movies and beyond (2021)
  • Author(s): 岩田想
  • Organizer: 第59回日本生物物理学会年会のサテライトイベント_PDB50周年記念シンポジウム
  • Invited
• [Presentation] GPCRの活性化機構とそのファインチューニング (2021)
  • Author(s): 岩田想
  • Organizer: 2021年度BINDSセミナー －成果と今後の展望－
  • Invited
• [Presentation] Proteins in action-高速分子動画法 (2021)
  • Author(s): 岩田想
  • Organizer: 次世代放射光サミット3rd International Forum for Innovation in Next Generation Synchrotron Radiation
  • Invited
• [Presentation] 抗体フラグメントを使った創薬ターゲット膜タンパク質の構造研究 (2021)
  • Author(s): 岩田想
  • Organizer: 創薬懇話会2021
  • Invited
• [Presentation] 高速分子動画法とその分子制御への応用 (2021)
  • Author(s): 岩田想
  • Organizer: 第77回顕微鏡学会学術講演会
  • Invited
• [Presentation] 高速分子動画法 (2021)
  • Author(s): 岩田想
  • Organizer: 生化学会中部支部例会
  • Invited
• [Presentation] Beyond the molecular movies (2021)
  • Author(s): 岩田想
  • Organizer: SACLA Users' Meeting
  • Invited
• [Presentation] 抗体フラグメントを用いたGPCRの構造解析と創薬への応用 (2020)
  • Author(s): 岩田想
  • Organizer: 第93回日本生化学会大会
  • Invited
• [Presentation] A Molecular Movie of Structural Changes in the Light-Driven Proton Pump Bacteriorhodopsin (2020)
  • Author(s): 岩田想
  • Organizer: 令和元年度 研究員会議総会・第21回 異分野交流の夕べ ポスター
  • Invited
• [Presentation] 膜タンパク質の細胞外ドメインを結合標的とする機能性ヒト抗体の高効率作製と構造デザイン (2020)
  • Author(s): 岩田想
  • Organizer: 令和元年度 創薬基盤推進研究事業 公開シンポジウム
  • Invited
• [Presentation] 高速分子動画法 (2019)
  • Author(s): 岩田想
  • Organizer: 第2回構造生命科学研究会
  • Invited
• [Presentation] Making Molecular Movies (2019)
  • Author(s): So Iwata
  • Organizer: RIKEN Europe Office Anniversary Symposium（RIKEN seminar）
  • Int'l Joint Research / Invited
• [Presentation] Proteins in Action (2019)
  • Author(s): So Iwata
  • Organizer: 18th IPR Retreat（蛋白研リトリート）
  • Invited
• [Presentation] 次世代構造創薬研究を先導するヒト膜タンパク質・抗体の生産技術支援 (2019)
  • Author(s): 岩田 想，野村紀通
  • Organizer: BINDS公開シンポジウム2019
• [Presentation] 膜タンパク質・抗体の高度生産技術を共役させた構造創薬研究 (2019)
  • Author(s): 岩田想
  • Organizer: 第2回モダリティ創薬デザイン研究会シンポジウム
  • Invited
• [Presentation] 「高速分子動画法」-自由電子レーザーを用いたX線結晶構造解析 (2019)
  • Author(s): 岩田想
  • Organizer: 2019年度iBIX-JAXA-KEK物構研-QST合同研究会
  • Invited
• [Presentation] 実験科学の新展開を情報科学に生かすために (2019)
  • Author(s): 岩田想
  • Organizer: CBI学会2019年大会
  • Invited
• [Presentation] Making molecular movies (2019)
  • Author(s): So Iwata
  • Organizer: 6th International Symposium on Diffraction Structural Biology :ISDSB2019
  • Int'l Joint Research / Invited
• [Presentation] 膜タンパク質構造研究：３次元から４次元へ (2019)
  • Author(s): 岩田想
  • Organizer: 第59回生物物理若手の会 夏の学校
  • Invited
• [Presentation] 膜タンパク質の細胞外ドメインを結合標的とする機能性抗体の高効率作製と構造デザイン (2019)
  • Author(s): 岩田想
  • Organizer: 鳥取大学-Trans Chromosomics共同研究成果発表会
  • Invited
• [Presentation] 立体構造から紐解く抗ヒスタミン薬の作用 (2019)
  • Author(s): 岩田想
  • Organizer: フォーサム2019京都 参天製薬共催ランチョンセミナー
  • Invited
• [Presentation] SACLA自由電子レーザーによるタンパク質分子動画法の現状と展望 / Molecular Movies of Proteins using SACLA: Current Status and Future (2019)
  • Author(s): 岩田想
  • Organizer: 第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会合同年次大会 WS「タンパク質が機能する瞬間を捉える: タンパク質ダイナミクス研究の新時代」
• [Presentation] Proteins in Action (2019)
  • Author(s): So Iwata
  • Organizer: 第24回 生物物理検討会（The 24th Biophysics Conference)
  • Int'l Joint Research / Invited
• [Presentation] 創薬ターゲット膜タンパク質構造研究と抗体を用いた機能制御 (2019)
  • Author(s): 岩田想
  • Organizer: （TALK）神戸医療産業都市推進機構
  • Invited
• [Book] “The Intervening Removable Affinity Tag (iRAT) System for the Production of Recombinant Antibody Fragments” in Methods Mol Biol. (2021)
  • Author(s): *Nomura N, Nomura Y, Sato Y and *Iwata S.
  • Total Pages: 340
  • Publisher: Humana Press
  • ISBN: 9781071611258
• [Book] Methods in Enzymology, Vol. 629, "Tumor Immunology and Immunotherapy; Molecular Methods" (Edited by Lorenzo Galluzzi, Nils-Petter Rudqvist) (2019)
  • Author(s): Norimichi Nomura, Yayoi Nomura, Yumi Sato, So Iwata
  • Total Pages: 511
  • Publisher: Academic Press
• [Remarks] B型肝炎ウイルスが感染受容体に結合するしくみを解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2024-01-18
• [Remarks] クライオ電子顕微鏡によりゴルジ体の亜鉛輸送体による亜鉛輸送機構の全容を解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2023-08-29-2
• [Remarks] 尿路結石形成を防ぐ腸内細菌で働く鍵分子・シュウ酸輸送体の立体構造解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2023-04-04
• [Remarks] 慢性アレルギー疾患に関わるヒスタミン受容体の構造解明―新規アトピー性皮膚炎・喘息治療薬の開発に貢献―
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2023-10-23
• [Remarks] 光回復酵素による損傷DNA修復反応を原子レベルで解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2023-12-01-0
• [Remarks] B型肝炎ウイルスの受容体“胆汁酸輸送体”の立体構造を解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2022-05-18
• [Remarks] B型肝炎ウイルス感染受容体であるヒト膜タンパク質の構造を解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2022-05-18-1
• [Remarks] 新型コロナウイルスのウイルス形成に必須の膜タンパク質の構造を解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2022-08-08
• [Remarks] 熱、炎症などに関与するプロスタグランジン受容体EP3シグナリング複合体の可視化
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2022-09-15
• [Remarks] スペルミジンはT細胞の脂肪酸酸化を直接活性化し老化による抗腫瘍免疫の低下を回復させる
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2022-10-28
• [Patent(Industrial Property Rights)] 皮膚筋炎又は間質性肺炎の患者の治療抵抗性の予測方法、及び当該方法に使用されるキット (2024)
  • Inventor(s): 笹井蘭、笹井恒雄、野中元裕、野村紀通
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2024-015255
  • Filing Date: 2024