Molecular soft interactions regulating membrane-interface activities in living systems

2008 Fiscal Year Final Research Report

• Project/Area Number: 15083101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: AKUTSU Hideo Osaka University, 蛋白質研究所, 招聘教授 (60029965)
• Co-Investigator(Kenkyū-buntansha): KODA Daisuke 九州大学, 生体防御医学研究所, 教授 (80186618) ; SHIMADA Ichio 東京大学, 大学院・薬学系, 教授 (70196476) ; MORIKAWA Kousuke 大阪大学, 蛋白質研究所, 客員教授 (80012665) ; HAGA Tatsuya 学習院大学, 理学部, 教授 (30011646) ; SHIRAKAWA Masahiro 京都大学, 大学院・工学研究科, 教授 (00202119) ; TOU Hiroyuki 九州大学, 生体防御医学研究所, 教授 (70192656) ; NISHIMURA Yoshifumi 横浜市大, 生命ナノシステム科学研究科, 教授 (70107390)
• Co-Investigator(Renkei-kenkyūsha): HAGA Tatsuya 学習院大学, 理学部, 教授 (30011646) ; SHIRAKAWA Masahiro 京都大学, 大学院・工学研究科, 教授 (00202119) ; TOU Hiroyuki 九州大学, 生体防御医学研究所, 教授 (70192656) ; NISHIMURA Yoshifumi 横浜市大, 生命ナノシステム科学研究科, 教授 (70107390)
• Project Period (FY): 2003 – 2009
• Keywords: 膜インターフェイス / 生命秩序 / ソフトな分子間相互作用 / 膜タンパク質 / シグナル伝達 / 物質輸送 / 核磁気共鳴法(NMR) / X線結晶構造解析

Research Abstract

本領域では生命に秩序をもたらす上で重要な役割を果たしている生体膜系に注目し、そこでタンパク質がどのような相互作用により、信号伝達、H^+-ATP合成酵素の回転、ミトコンドリア膜でのタンパク質輸送等を制御しているのかを研究し、ソフトな分子間相互作用が重要な役割を果たしていることを明らかにした。また、巨大な分子あるいは分子複合体とリガンドタンパク質の相互作用を解析するための研究法の開発、生体膜、生きたヒト細胞におけるタンパク質の構造解析法の開発等でも顕著な成果を上げた。

Research Products

• [Journal Article] Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling. (2009)
  • Author(s): H. Ohnishi, H. Tochio, Z. Kato, K. Orii, A. Li, T. Kimura, H. Hiroaki, N. Kondo, M. Shirakawa
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 10260-10265
  • Peer Reviewed
• [Journal Article] Structural basis of yeast Tim40/Mia40 as an oxidative translocator in the mitochondrial intermembrane space. (2009)
  • Author(s): S. Kawano, K. Yamano, M. Naoe, T. Momose, K. Terao, S. Nishikawa, N. Watanabe, T. Endo
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 14403-14407
  • Peer Reviewed
• [Journal Article] Observation of NMR signals from proteins introduced into living mammalian cells by reversible membrane permeabilization using a pore-forming toxin (2009)
  • Author(s): S. Ogino, S. Kubo, R. Umemoto, S. Huang, N. Nishida, I. Shimada
  • Journal Title: Streptolysin O.J. Am. Chem. Soc. 131 Pages: 10834-10835
  • Peer Reviewed
• [Journal Article] High-resolution multi-dimensional NMR spectroscopy of proteins in human cells. (2009)
  • Author(s): K. Inomata, A. Ohno, H. Tochio, S. Isogai, T. Tenno, I. Nakase, T. Takeuchi, S. Futaki, Y. Ito, H. Hiroaki, M. Shirakawa
  • Journal Title: Nature 458 Pages: 106-109
  • Peer Reviewed
• [Journal Article] Protein structure determination in living cells by in-cell NMR spectroscopy. (2009)
  • Author(s): D. Sakakibara, A. Sasaki, T. Ikeya, J. Hamatsu, T. Hanashima, M. Mishima, M. Yoshimasu, N. Hayashi, T. Mikawa, M. Walchli, B.O. Smith, M. Shirakawa, P. Guntert, Y. Ito
  • Journal Title: Nature 458 Pages: 102-105
  • Peer Reviewed
• [Journal Article] Structure, interaction, and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G (2009)
  • Author(s): A. Furukawa, T. Nagata, A. Matsugami, Y. Habu, R. Sugiyama, F. Hayashi, S. Yokoyama, H. Takaku, M. Katahira
  • Journal Title: EMBO J. 28 Pages: 440-451
  • Peer Reviewed
• [Journal Article] Stepwise propagation of the ATP-induced conformational change of the F1-ATPaseβsubunit revealed by NMR. (2009)
  • Author(s): H. Yagi, N. Kajiwara, T. Iwabuchi, K. Izumi, M. Yoshida, H. Akutsu
  • Journal Title: J. Biol. Chem. 284 Pages: 2307-2319
  • Peer Reviewed
• [Journal Article] Crystal structure of the conserved N-terminal domain of the proxisomal matrix protein import receptor, Pex14p (2009)
  • Author(s): J.R. Su, K. Takeda, S. Tamura, Y. Fujiki *K. Miki
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 417-421
  • Peer Reviewed
• [Journal Article] A helix-to-coil transition at theε-cut site in the transmembrane dimer of the amyloid precursor protein is required for proteolysis (2009)
  • Author(s): T. Sato, T. -C. Tang, G. Reubins, J.Z. Fei, T. Fujimoto, P. Kienlen-Campard, S.N. Constantinescu, J. -N. Octave, S. Aimoto, S.O. Smith
  • Journal Title: Proc. Natl Acad. Sci. USA 106 Pages: 1421-1426
  • Peer Reviewed
• [Journal Article] The nature of the TRAP-Anti-TRAP complex (2009)
  • Author(s): M. Watanabe, J.G. Heddle, K. Kikuchi, S. Unzai, S. Akashi, S.Y. Park, J.R. Tame
  • Journal Title: Proc. Natl. Acad. Sci. U S A 106 Pages: 2176-2181
  • Peer Reviewed
• [Journal Article] Dual Functional Probe to Detect Protease Activity for Fluorescence Measurement and 19F MRI (2009)
  • Author(s): S. Mizukami, R. Takikawa, F. Sugihara, M. Shirakawa K. Kikuchi
  • Journal Title: Angew. Chem. Int. Ed. 48 Pages: 3641-3643
  • Peer Reviewed
• [Journal Article] Gibberellin-induced DELLA recognition by the gibberellin receptor GID1. (2008)
  • Author(s): K. Murase, Y. Hirano, T. -p. Sun, T. Hakoshima
  • Journal Title: Nature 456 Pages: 459-464
  • Peer Reviewed
• [Journal Article] A magic-angle-spinning NMR method for ^1H-^1H distance measurement using coherent polarization transfer in ^<13>C-labeled organic solids. (2008)
  • Author(s): H. Takahashi, H. Akutsu, T. Fujiwara
  • Journal Title: J. Chem. Phys. 129 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Structure-guided identification of a new catalytic motif of oligosaccharyltransferase. (2008)
  • Author(s): Igura M, Maita N, Kamishikiryo J, Yamada M, Obita T, Maenaka K, Kohda, D
  • Journal Title: EMBO J 27 Pages: 234-243
  • Peer Reviewed
• [Journal Article] Mg2+-sensing mechanism of Mg2+ transporter MgtE probed by molecular dynamics study (2008)
  • Author(s): R. Ishitani, Y. Sugita, N. Dohmae, N. Furuya, M. Hattori O. Nureki
  • Journal Title: Proc. Natl. Acad. Sci. USA. 105 Pages: 15393-15398
  • Peer Reviewed
• [Journal Article] Conformational transition of Sec machinery inferred from bacterial SecYE structures (2008)
  • Author(s): T. Tsukazaki, H. Mori, S. Fukai, R. Ishitani, T. Mori, N. Dohmae, A. Perederina, Y. Sugita, D.G. Vassylyev, K. Ito O. Nureki
  • Journal Title: Nature 455 Pages: 988-992
  • Peer Reviewed
• [Journal Article] Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains (2008)
  • Author(s): Y. Sato, A. Yoshikawa, A. Yamagata, H. Mimura, M. Yamashita, K. Ookata, O. Nureki, K. Iwai, M. Komada S. Fuka
  • Journal Title: Nature 455 Pages: 358-362
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Ladder-shaped Tetracyclic, Heptacyclic, and Decacyclic Ethers and Evaluation of the Interaction with Transmembrane Proteins (2008)
  • Author(s): K. Torikai, T. Oishi, S. Ujihara, N. Matsumori, K. Konoki, M. Murata, S. Aimoto
  • Journal Title: J. Am. Chem. Soc. 130 Pages: 10217-26
  • Peer Reviewed
• [Journal Article] The structural basis for an essential subunit interaction in influenza virus RNA polymerase (2008)
  • Author(s): E. Obayashi, H. Yoshida, F. Kawai, N. Shibayama, A. Kawaguchi, K. Nagata, J.R. Tame, S.Y. Park
  • Journal Title: Nature 454 Pages: 1127-1131
  • Peer Reviewed
• [Journal Article] IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade (2008)
  • Author(s): H. Nojima, M. Adachi, T. Matsui, K. Okawa, Sh. Tsukita Sa. Tsukita
  • Journal Title: Nat Cell Biol 10 Pages: 971-978
  • Peer Reviewed
• [Journal Article] Jellyfish vision starts with cAMP signaling mediated by opsin-Gs cascade (2008)
  • Author(s): M. Koyanagi, K. Takano, H. Tsukamoto, K. Ohtsu, F. Tokunaga A Terakita
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 15576-1558037
  • Peer Reviewed
• [Journal Article] Multiple-state reactions between the epidermal growth factor receptor and Grb2 as observed using single-molecule analysis. (2007)
  • Author(s): M. Morimatsu, H. Takagi, K.G. Ota, R. Iwamoto, T. Yanagida, Y. Sako
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 18013-18018
  • Peer Reviewed
• [Journal Article] Structure of the light-harvesting bacteriochlorophyll c assembly in chlorosomes from Chlorobium limicola determined by solid-state NMR (2007)
  • Author(s): A. Egawa, T. Fujiwara, T. Mizoguchi, Y. Kakitani, Y. Koyama H. Akutsu
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 790-795
  • Peer Reviewed
• [Journal Article] Structures of the thermophilic F1-ATPaseεsubunit suggesting ATP-regulated arm motion of its C-terminal domain in F1 (2007)
  • Author(s): H. Yagi, N. Kajiwara, H. Tanaka, T. Tsukihara, Y. Kato-Yamada, M. Yoshida H. Akutsu
  • Journal Title: Proc. NatI. Acad. Sci. USA 104 Pages: 11233-11238
  • Peer Reviewed
• [Journal Article] Tom20 recognizes mitochondrial presequences through 5 dynamic equilibrium among multiple bound states. (2007)
  • Author(s): T. Saitoh, M. Igura, T. Obita, T. Ose, R. Kojima, K. Maenaka, T. Endo, D. Kohda
  • Journal Title: EMBO J 26 Pages: 777-4787
  • Peer Reviewed
• [Journal Article] Crystal structure of measles virus hemagglutinin provides insight into effective vaccines. (2007)
  • Author(s): T. Hashiguchi, M. Kajikawa, N. Maita, M. Takeda, K. Kuroki, K. Sasaki, D. Kohda, Y. Yanagi, *K. Maenaka
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 19535-19540
  • Peer Reviewed
• [Journal Article] Structural Basis of the Collagen-binding Mode of Discoidin Domain Receptor 2. (2007)
  • Author(s): O. Ichikawa, M. Osawa, N. Nishida, N. Goshima, N. Nomura, I. Shimada
  • Journal Title: EMBO.J. 26 Pages: 4168-4176
  • Peer Reviewed
• [Journal Article] Structure of the extracellular regions of the group II/III metabotropic glutamate receptors (2007)
  • Author(s): T. Muto, D. Tsuchiya, *K. Morikawa H. Jingami
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 3759-3764
  • Peer Reviewed
• [Journal Article] Crystal structure of the MgtE Mg2+ transporter (2007)
  • Author(s): M. Hattori, Y. Tanaka, S. Fukai, R. Ishitani O. Nureki
  • Journal Title: Nature 448 Pages: 1072-1075
  • Peer Reviewed
• [Journal Article] Single-molecule analysis of epidermal growth factor binding on the surface of living cells. (2006)
  • Author(s): Y. Teramura, J. Ichinose, H. Takagi, K. Nishida, T. Yanagida, Y. Sako
  • Journal Title: EMBO J. 25 Pages: 4215-4222
  • Peer Reviewed
• [Journal Article] Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d) (2006)
  • Author(s): M. Shiroishi, K. Kuroki, L. Rasubala, K. Tsumoto, I. Kumagai, E. Kurimoto, K. Kato, D. Kohda, K. Maenaka
  • Journal Title: Proc. Natl. Acad. Sci. U S A. 103 Pages: 16412-16417
  • Peer Reviewed
• [Journal Article] NMR solution structure of the tandem SH3 domains of p47phox complexed with a p22phox derived proline-rich peptide. (2006)
  • Author(s): K. Ogura, I. Nobuhisa, S. Yuzawa, R. Takeya, S. Torikai, K. Saikawa, H. Sumimoto, *F. Inagaki
  • Journal Title: J. Biol. Chem. 281 Pages: 3660-3668
  • Peer Reviewed
• [Journal Article] Protonation of the acidic residues in the transmembrane cation-binding sites of the Ca2+-pump (2005)
  • Author(s): Y. Sugita, N. Miyashita, M. Ikeguchi, A. Kidera C. Toyoshima
  • Journal Title: J. Am. Chem. Soc. 127 Pages: 6150-6151
  • Peer Reviewed
• [Journal Article] Structure of the rotor of the V-Type Na+-ATPase from Enterococcus hirae. (2005)
  • Author(s): T. Murata, I. Yamato, Y. Kakinuma, A.G. Leslie J.E. Walker
  • Journal Title: Science. 308 Pages: 654-659
  • Peer Reviewed
• [Journal Article] Translocation of a long amino-terminal domain through ER membrane mediated by following signal-anchor sequence (2005)
  • Author(s): Y. Kida, K. Mihara M. Sakaguchi
  • Journal Title: EMBO J. 24 Pages: 3202-3213
  • Peer Reviewed
• [Journal Article] Crystal Structure of thymine DNA glycosylase conjugated to SUMO-1. (2005)
  • Author(s): D. Baba, N. Maita, J. -G. Jee, Y. Uchimura, H. Saitoh, K. Sugasawa, F. Hanaoka, H. Tochio, H. Hiroaki, *M. Shirakawa
  • Journal Title: Nature 435 Pages: 979-982
  • Peer Reviewed
• [Journal Article] G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration. (2005)
  • Author(s): N. Mizuno, H. Kokubu, M. Sato, A. Nishimura, J. Yamauchi, H. Kurose, H. Itoh
  • Journal Title: Proc. Natl. Acad. Sci. USA. 102 Pages: 12365-12370
  • Peer Reviewed
• [Journal Article] Ligand-induced Rearrangement of the dimeric metabotropic glutamate receptor 1α. (2004)
  • Author(s): M. Tateyama, H. Abe, H. Nakata, O. Saitoh, Y. Kubo
  • Journal Title: Nature Struc. Mol. Biol. 11 Pages: 637-642
  • Peer Reviewed
• [Journal Article] A Conformational Change of H+-ATPaseβMonomer Revealed on Segmental Isotope Labeling NMR Spectroscopy (2004)
  • Author(s): H. Yagi, T. Tsujimoto, T. Yamazaki, M. Yoshida, H. Akutsu
  • Journal Title: J. Am. Chem. Soc. 126 Pages: 16632-16638
  • Peer Reviewed
• [Journal Article] Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi. (2004)
  • Author(s): H. Hirose, K. Arasaki, N. Dohmae, K. Takio, K. Hatsuzawa, M. Nagahama, K. Tani, A. Yamamoto, M. Tohyama M. Tagaya
  • Journal Title: EMBO J. 23 Pages: 1267-1278
  • Peer Reviewed
• [Journal Article] Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion. (2004)
  • Author(s): K. Nakajima, H. Hirose, M. Taniguchi, H. Kurashina, K. Arasaki, M. Nagahama, K. Tani, A. Yamamoto *M. Tagaya
  • Journal Title: EMBO J. 23 Pages: 3216-3226
  • Peer Reviewed
• [Presentation] Molecular Dynamics Study of Sarcoplasmic Reticulum Calcium Pump (2008)
  • Author(s): Yuji Sugita
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会(BMB2008)
  • Place of Presentation: 神戸ポートピアホテル、神戸市
  • Year and Date: 2008-12-09
• [Presentation] Theoretical Analysis and Application of Transferred Cross-saturation Methods (2008)
  • Author(s): Ichio Shimada
  • Organizer: the 49th ENC, Asilomar, California
  • Place of Presentation: USA
  • Year and Date: 2008-03-14
• [Presentation] Structural studies of Root effect hemoglobins (2006)
  • Author(s): Takeshi Yokoyama, Satoru Unzai, Sam-Yong 6 Park,, *Jeremy R.H. Tame.
  • Organizer: The XIVth International Conference on Dioxygen Binding and Sensing Proteins
  • Place of Presentation: Anton Dohn Zoological Station, Naples, Italy
  • Year and Date: 20060903-20060907
• [Presentation] Structural determination of biological supramolecular systems by CP/MAS solid-state NMR (2006)
  • Author(s): Hideo Akutsu, Toshimicih Fujiwara
  • Organizer: XXIInd International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: Gottingen
  • Year and Date: 20060820-20060825
• [Presentation] Effect of G proteinβγsubunits on the interaction of the muscarinic acetylcholine receptor M2 or M4 subtype with G protein Gαi1 subunit (2006)
  • Author(s): Ichiyama, S., Nemoto, R., Tanabe, H., Okamura, M., Furukawa, H., Haga, T.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOB Congress
  • Place of Presentation: Kyoto International Conference Hall, Kyoto, Japan)
  • Year and Date: 20060618-20060623
• [Presentation] Cracking of the targeting signal embedded in mitochondrial presequences (2005)
  • Author(s): Daisuke Kohda
  • Organizer: XX Congress of the International Union of Crystallography
  • Place of Presentation: Florence, Italy
  • Year and Date: 20050823-20050831
• [Presentation] High-resolution NMR in biological systems (2004)
  • Author(s): Masahiro Shirakawa, Jun Kikuchi, JunGoo Gee, Yutaka Ito, Takahisa Ikegami, Masaki Mishima
  • Organizer: the 2004 meeting of the International Society for Magnetic Resonance in Medicine
  • Place of Presentation: 京都市
  • Year and Date: 2004-05-16
• [Book] 生体の科学(不溶性の細胞外マトリックスとの相互作用を解明する新しいNMR測定法) (2008)
  • Author(s): 西田紀貴・嶋田一夫
  • Total Pages: 358-59
• [Book] 実験化学講座(日本化学会編8, 5.2.1たんぱく質, 第5版 8 NMR・ESR) (2006)
  • Author(s): 杤尾豪人、白川昌宏
  • Total Pages: 287-305
  • Publisher: 丸善株式会社
• [Book] G Protein-Coupled Receptors(Structure, Function, and Ligand Screening) (2006)
  • Author(s): Haga, T., Takeda, S., ed.
  • Total Pages: 315
  • Publisher: CRC Press, Taylor & Francis Group
• [Book] 蛋白質核酸酵素(阿久津秀雄、月原冨武、嶋田一夫編, 生命秩序を担う生体超分子, H^+-ATP 合成酵素F_1 の回転駆動力は何か, 増刊 50 巻10 号) (2005)
  • Author(s): 分担 八木宏昌、阿久津秀雄
  • Total Pages: 1160-1166
  • Publisher: 共立出版
• [Book] 蛋白質・核酸・酵素(生命秩序を担う生体超分子,カルシウムポンプの構造と機能, 増刊号, 50) (2005)
  • Author(s): 杉田有治, 豊島近
  • Total Pages: 1271-1277
• [Book] 蛋白質核酸酵素(生命秩序を担う生体超分子, 8月号増刊) (2005)
  • Author(s): 雲財悟、朴三用、Jeremy R.H. Tame
  • Total Pages: 1322-1327
  • Publisher: 共立出版
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/biophys/priority/index.html
• [Patent(Industrial Property Rights)] 希土類発光プローブ発明者:菊地和也, 水上進, 東内一博 (2008)
  • Inventor(s): 菊地和也, 水上進, 東内一博
  • Industrial Property Number: 特願2008-61320
  • Filing Date: 2008-03-11
• [Patent(Industrial Property Rights)] NMR測定方法および該方法に用いるための構造物 (2008)
  • Inventor(s): 児嶋長次郎, 林俊達, 三島正規, 河野俊之
  • Industrial Property Number: 特許第4147083号
  • Filing Date: 2008-06-27
• [Patent(Industrial Property Rights)] クマリン誘導体及びそれを含む蛍光プローブ (2007)
  • Inventor(s): 菊地和也, 水上進, 木村聡志
  • Industrial Property Number: 特願2007-59057
  • Filing Date: 2007-03-08
• [Patent(Industrial Property Rights)] MRI用プローブ (2007)
  • Inventor(s): 菊地和也, 水上進, 滝川利佳, 白川昌宏
  • Industrial Property Number: 特願2007-27395
  • Filing Date: 2007-10-22
• [Patent(Industrial Property Rights)] 免疫細胞刺激活性を有する機能ペプチド (2006)
  • Inventor(s): 向井秀仁, 若松馨
  • Industrial Property Number: 特願2006-267559
  • Filing Date: 2006-09-29
• [Patent(Industrial Property Rights)] ペプチドエステルを用いたライゲーション法、およびチオエステル化合物の製造方法 (2005)
  • Inventor(s): 相本三郎, 川上徹
  • Industrial Property Number: 特願2005-3000947
  • Filing Date: 2005-10-14