Structural study of signal transduction by membrane receptors through protein-protein interactions

2008 Fiscal Year Final Research Report

• Project/Area Number: 15083102
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University (2004-2008); Yokohama City University (2003)
• Principal Investigator: SHIRAKAWA Masahiro Kyoto University, 大学院・工学研究科, 教授 (00202119)
• Project Period (FY): 2003 – 2008
• Keywords: NMR / 結晶構造解析 / 膜たんぱく質

Research Abstract

本研究期間中に、チミンDNAグリコシラーゼ(TDG)についてSUMO-3化されたTDGの中央領域の立体構造を論文発表し、非共役型のSUMO-1/TDGの中央領域の立体構造、を解析した。またMCAF1のSUMO結合領域(SIM)とSUMO-3の複合体の立体構造をNMRにより決定した。岐阜大学医学研究科の加藤善一郎博士らとの共同研究により、Myd88のTIRドメインの立体構造をNMRによって決定し、さらにシグナル伝達に関与する分子表面残基を解析した。

Research Products

• [Journal Article] Dual-Function Probe to Detect Protease Activity for Fluorescence Measurement and 19F MRI. (2009)
  • Author(s): Mizukami, S., Takikawa, R., Sugihara, F., Shirakawa, M. and Kikuchi, K.
  • Journal Title: Angewandte Chemie International Edition (Published Online)
• [Journal Article] High-resolution multi-dimensional NMR spectroscopy of proteins in human cells. (2009)
  • Author(s): Inomata, K., Ohno, A., Tochio, H., Isogai, S., Tenno, T., Nakase, I., Takeuchi, T., Futaki, S., Ito, Y., Hiroaki, H, and Shirakawa, M.
  • Journal Title: Nature 458 Pages: 106-109
• [Journal Article] Protein structure determination in living cells by in-cell NMR spectroscopy. (2009)
  • Author(s): Sakakibara, D., Sasaki, A., Ikeya, T., Hamatsu, J., Hanashima, T., Mishima, M., Yoshimasu, M., Hayashi, N., Mikawa, T., Walchli, M., Smith, B. O., Shirakawa, M., Guntert, P. and Ito, Y.
  • Journal Title: Nature 458 Pages: 102-105
• [Journal Article] Molecular basis for SUMOylation-dependent regulation of DNA binding activity of Heat Shock Factor 2. (2009)
  • Author(s): Tateishi, Y., Ariyoshi, M., Igarashi, R., Hara, H., Mizuguchi, K., Seto, A., Nakai, A., Kokubo, T., Tochio, H. and Shirakawa, M.
  • Journal Title: Journal of Biological Chemistry 284 Pages: 2435-2447
• [Journal Article] Structure of the SUMO-interacting motif of MBD1-containing chromatin associated factor 1 (MCAF1) bound to SUMO-3. (2008)
  • Author(s): Sekiyama, N., Ikegami, T., Yamane, T., Ikeguchi, M., Uchimura, Y., Baba, D., Ariyoshi, M., Tochio, H., Saitoh, H. and Shirakawa, M.
  • Journal Title: Journal of Biological Chemistry 283 Pages: 35966-35975
• [Journal Article] Hemi-methylated DNA recognition by the SRA protein Np95 via a base flipping mechanism. (2008)
  • Author(s): Arita, K., Ariyoshi, M., Tochio, H., Nakamura, Y. and Shirakawa, M.
  • Journal Title: Nature 455 Pages: 818-821
• [Journal Article] The solution structure of the C-terminal domain of NfeD reveals a novel membrane-anchored OB-fold. (2008)
  • Author(s): Kuwahara, Y., Ohno, A., Morii, T., Yokoyama, H., Matsui, I., Tochio, H., Shirakawa, M., and Hiroaki, H.
  • Journal Title: Protein Science 17 Pages: 1915-1924
• [Journal Article] Expression, purification, and a structural analysis of human IL-18 binding protein : A potent therapeutic molecule for allergy. (2008)
  • Author(s): Kimura, T., Kato, Z., Ohnishi, H., Tochio, H., Shirakawa, M., Kondo, N.
  • Journal Title: Allergology International 4 Pages: 367-.376
• [Journal Article] Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5. (2008)
  • Author(s): Goda, N., Tenno, T., Inomata, K., Shirakawa, M., Tanaka, T., Hiroaki, H.
  • Journal Title: Experimental Cell Research 314 Pages: 2352-2361
• [Journal Article] Kinetic and Thermodynamic evidence for flipping of a methyl-CpG binding domain on methylated DNA. (2008)
  • Author(s): Inomata, K., Ohki, I., Tochio, H., Fujiwara, K., Hiroaki, H., Shirakawa, M.
  • Journal Title: Biochemistry 47 Pages: 3266-3271
• [Journal Article] Paramagnetic Relaxation-Based 19F MRI Probe to Detect Protease. (2008)
  • Author(s): Mizukami, S., Takikawa, R., Sugihara, F., Hori, Y., Tochio, H., Waelchli, M., Shirakawa, M., Kikuchi, K.
  • Journal Title: Activity Journal of the American Chemical Society 130 Pages: 794-795
• [Journal Article] Structural Analysis of Pituitary Adenylate Cyclase-Activating polypeptides Bound to Phospholipid embranes by Magic Angle Spinning Solid-State NMR. (2007)
  • Author(s): Komi, N., Okawa, K., Tateishi, Y., Shirakawa, M., Fujiwara, T., Akutsu, H.
  • Journal Title: Biochimica et Biophysica Acta -Biomembranes 1768 Pages: 3001-3011
• [Journal Article] Fluoroscopic assessment of protein leakage during Xenopus oocytes in-cell NMR experiment by co-injected EGFP. (2007)
  • Author(s): Sakai, T., Tochio, H., Inomata, K., Sasaki, Y., Tenno, T., Tanaka, T., Kokubo, T., Hiroaki, H., Shirakawa, M.
  • Journal Title: Analytical Biochemistry 371 Pages: 247-249
• [Journal Article] Characterization of the sequence specificity of the R1Bm endonuclease domain by structural and biochemical studies. (2007)
  • Author(s): Maita, N., Aoyagi, H., Osanai, M., Shirakawa, M., Fujiwara, H.
  • Journal Title: Nucleic Acid Research 35 Pages: 3918-3927
• [Journal Article] Magnetic resonance-based visualization of gene expression in mammalian cells using a bacterial polyphosphate kinase reporter gene. (2007)
  • Author(s): Ki, S., Sugihara, F., Kasahara, K., Tochio, H., Shirakawa, M. and Kokubo, T.
  • Journal Title: Biotechniques 42 Pages: 209-215
• [Journal Article] LBT/PTD dual tagged vector for purification, cellular protein delivery and visualization in living cells. (2007)
  • Author(s): Goda, N., Tenno, T., Inomata, K., Iwaya, N., Sasaki, Y., Shirakawa, M., Hiroaki, H.
  • Journal Title: Biochemica et Biophysica Acta 1773 Pages: 141-146
• [Journal Article] Distance determination in human ubiquitin by pulse double electron resonance and double quantum coherence ESR methods. (2007)
  • Author(s): Hara, H., Tenno, T. and Shirakawa, M.
  • Journal Title: Journal of Magnetic Resonance 184 Pages: 78-84
• [Journal Article] Fine-tuning of protein domain boundary by minimizing potential coiled coil regions. (2007)
  • Author(s): Iwaya, N., Goda, N., Unzai, S., Fujiwara, K., Tanaka, T., Tomii, K., Tochio, H., Shirakawa, M. and Hiroaki, H.
  • Journal Title: Journal of biomolecular NMR 37 Pages: 53-63
• [Journal Article] In-Cell NMR Spectroscopy of Proteins inside Xenopus laevis Oocytes. (2006)
  • Author(s): Sakai, T., Tochio, H., Tenno, T., Ito, Y., Kokubo, T., Hiroaki, H. and Shirakawa, M.
  • Journal Title: Journal of biomolecular NMR 36 Pages: 179-188
• [Journal Article] Crystal structure of SUMO-3-modified thymine-DNA glycosylase. (2006)
  • Author(s): Baba, D., Maita; N., Jee, J.-G., Uchimura, Y., Saitoh, H., Sugasawa, K., Hanaoka, F., Tochio, H., Hiroaki, H, Shirakawa, M.
  • Journal Title: Journal of Molecular Biology 359 Pages: 137-147
• [Journal Article] novel magnetic resonance-based method to measure gene expression in living cells. (2006)
  • Author(s): Ki, S., Sugihara, F., Kasahara, K., Tochio, H., Okada-Marubayashi, A., Tomita, S., Morita, M., Ikeguchi, M., Shirakawa, M. and Kokubo, T.
  • Journal Title: Nucleic Acid Research 34 Pages: e51
• [Journal Article] The structure of the third intracellular loop of the muscarinic acetylcholine receptor M2 subtype. (2006)
  • Author(s): Ichiyama, S., Oka, Y., Haga, K., Kojima, S., Tateishi, Y., Shirakawa, M., and Haga, T.
  • Journal Title: FEBS Letter 580 Pages: 23-26
• [Journal Article] Crystal Structure of thymine DNA glycosylase conjugated to SUMO-1. (2005)
  • Author(s): Baba, D., Maita, N., Jee, J.-G., Uchimura, Y., Saitoh, H., Sugasawa, K., Hanaoka, F., Tochio, H., Hiroaki, H., Shirakawa, M.
  • Journal Title: Nature 435 Pages: 979-982
• [Journal Article] The UBL-UBA protein KPC2 is required for degradation of p27 at G1 phase. (2005)
  • Author(s): Hara, T., Kamura, T., Kotoshiba, S., Fujiwara, K., Onoyama, I., Shirakawa, M. and Nakayama, K.-I.
  • Journal Title: Molecular and Cellular Biology 25 Pages: 9292-303
• [Journal Article] Molecular mechanism of a temperature-sensitive phenotype in peroxisomal biogenesis disorder. (2005)
  • Author(s): Hashimoto, K., Kato, Z., Nagase, T., Shimozawa, N., Kuwata, K., Omoya, K., Li, A., Matsukuma, E., Yamamoto, Y., Ohnishi, H., Tochio, H., Shirakawa, M., Suzuki, Y., Wanders, R. J. A., Kondo, N.
  • Journal Title: Pediatric Research 58 Pages: 263-9
• [Journal Article] Structural characterization of the MIT domain from human Vps4b. (2005)
  • Author(s): Takasu, H., Jee, J. G., Ohno, A., Goda, N., Fujiwara, K., Tochio, H., Shirakawa, M., and Hiroaki, H.
  • Journal Title: Biochemical and Biophysical Research Communications 334 Pages: 460-465
• [Journal Article] Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling.
  • Author(s): Ohnishi, H., Tochio, H., Kato, Z., Orii, K., Li, A., Kimura, T., Hiroaki,H., Kondo, N., and Shirakawa, M.
  • Journal Title: Proceedings of the National Academy of Science (in press)
• [Presentation] In-cell NMRによる細胞質内タンパク質の構造、機能解析 (2008)
  • Author(s): 白川昌宏
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] In-cell NMRによる細胞内タンパク質の構造、機能の観察 (2008)
  • Author(s): 白川昌宏
  • Organizer: 第8回日本蛋白質科学会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-11
• [Presentation] NMRとMRIを使った細胞内反応の非侵襲計測 (2007)
  • Author(s): 白川昌宏
  • Organizer: 日本化学会第87春季年会
  • Place of Presentation: 大阪
  • Year and Date: 2007-03-29
• [Presentation] SUMO化によるチミンDNAグリコシラーゼ機能調整 (2006)
  • Author(s): 白川昌宏
  • Organizer: 第6回日本蛋白質科学会年会
  • Place of Presentation: 京都
  • Year and Date: 2006-04-26
• [Presentation] SUMOコードの謎を解く (2005)
  • Author(s): 白川昌宏
  • Organizer: 第28回分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2005-12-10
• [Presentation] 蛋白質修飾による蛋白質の構造変化を捉える-ユビキチン化・SUMO化蛋白質の調製とX線構造解析 (2005)
  • Author(s): 白川昌宏
  • Organizer: 日本結晶学会2005年度年会
  • Place of Presentation: 姫路
  • Year and Date: 2005-12-07
• [Presentation] SUMO化による蛋白質の機能・構造変換の構造学的研究 (2004)
  • Author(s): 白川昌宏
  • Organizer: 第27回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2004-12-08
• [Presentation] NMR structural biology of protein-nucleic acid recognition (2004)
  • Author(s): 白川昌宏
  • Organizer: 第43回NMR討論会
  • Place of Presentation: 東京
  • Year and Date: 2004-11-11
• [Presentation] 化学修飾による核内制御-DNAメチル化とたんぱく質のユビキチン化 (2004)
  • Author(s): 白川昌宏
  • Organizer: 日本薬学会124年会
  • Place of Presentation: 大阪
  • Year and Date: 2004-03-30
• [Presentation] SUMO化による蛋白質の機能変換の構造学的研究 (2003)
  • Author(s): 白川昌宏
  • Organizer: 第26回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2003-12-11
• [Presentation] uaternary structure of polyubiquitin chains (2003)
  • Author(s): 白川昌宏
  • Organizer: 第76回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2003-10-17
• [Book] 5.2.1たんぱく質 実験化学講座第5版 日本化学会編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
• [Patent(Industrial Property Rights)] 変異導入MyD88蛋白によるToll様受容体/インターロイキン18シグナルの特異的制御法 (2007)
  • Inventor(s): 近藤直実、加藤善一郎、大西秀典、白川昌宏、杤尾豪人
  • Industrial Property Rights Holder: 財団法人大阪産業振興機構、国立大学法人大阪大学、国立大学法人京都大学
  • Industrial Property Number: 特願2007-200776
  • Filing Date: 2007-08-01
• [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 Rights Holder: 財団法人大阪産業振興機構、国立大学法人大阪大学、国立大学法人京都大学
  • Industrial Property Number: 特願2007-273956
  • Filing Date: 2007-10-22