A1蛋白質-テロメア-テロメレース3者複合体の構造解析とテロメレース阻害法の開発

2011 年度 研究成果報告書

• 研究課題/領域番号: 21370047
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 構造生物化学
• 研究機関: 京都大学 (2010-2011); 横浜市立大学 (2009)
• 研究代表者: 片平 正人 京都大学, エネルギー理工学研究所, 教授 (70211844)
• 研究分担者: 永田 崇 京都大学, エネルギー理工学研究所, 助教 (10415250)
• 研究期間 (年度): 2009 – 2011
• キーワード: テロメア / テロメラーゼ / A1タンパク質 / 癌 / デコイ

研究概要

A1タンパク質と同じRRM型に属するMusashiタンパク質に関し、標的RNAとの複合体の立体構造を、ロングレンジの構造情報を活かす事で決定する事に成功した。この手法でA1蛋白質-テロメア-テロメレース3者複合体の構造解析を行った結果、A1タンパク質はテロメアDNAとテロメラーゼRNAをブリッジしている事が分かった。これよりA1はテロメラーゼをテロメアDNAまでリクルートする働きを持つ事が示唆された。さらにデコイ核酸によるテロメレース阻害戦略の有効性も示唆された。

研究成果

• [雑誌論文] Structure of Musashi1 in a complex with target RNA : The role of aromatic stacking interactions (2012)
  • 著者名/発表者名: Ohyama, T., Nagata, T., Tsuda, K., Kobayashi, N., Imai, T., Okano, H., Yamazaki, T. and Katahira, M
  • 雑誌名: Nucleic Acids Res 巻: 10 ページ: 3218-3231
  • DOI: doi:10.1093/nar/gkr1139
  • 査読あり
• [雑誌論文] Intelligent ribozyme that switches its activity in response to K+ throughquadruplex formation (2012)
  • 著者名/発表者名: Nagata, T., Sakurai, Y., Hara, Y., Mashima, T. and Katahira, M.
  • 雑誌名: FEBS J. 巻: 279 ページ: 1456-1463
  • DOI: doi:10.1111/j.1742-4658.2012.08538.x
  • 査読あり
• [雑誌論文] Presence of alternating glucosaminoglucan in the sheath of Thiothrix nivea (2012)
  • 著者名/発表者名: Takeda, M., Kondo, K., Ymamada, M., Sumikawa, M., Koizumi, J., Mashima, T. and Katahira, M.
  • 雑誌名: Internet J. Biol. 巻: 50 ページ: 236-244
  • DOI: doi:10.1016/j.ijbiomac.2011.10.024
  • 査読あり
• [雑誌論文] Structural aspects for the recognition of ATPby ribonucleopeptide receptors (2011)
  • 著者名/発表者名: Nakano, S., Mashima, T., Matsugami, A., Inoue, M., Katahira, M. and Morii, T.
  • 雑誌名: J. Am. Chem. Soc. 巻: 133 ページ: 4567-4579
  • DOI: DOI:10.1021/ja110725d
  • 査読あり
• [雑誌論文] Heat shock protein 70 inhibitsHIV-1 Vif-mediated ubiquitination and degradation of APOBEC3G (2011)
  • 著者名/発表者名: Sugiyama, R., Nishitsuji, H., Furukawa, A., Katahira, M., Habu, Y., Takeuchi, H., Ryo, A. and Takaku, H.
  • 雑誌名: J. Biol. Chem. 巻: 286 ページ: 10051-10057
  • DOI: doi:10.1074/jbc.M110.166108
  • 査読あり
• [雑誌論文] Study of a novel glycoconjugate, thiopeptidoglycan, and a novel polysaccharide lyase (2011)
  • 著者名/発表者名: Kondo, K., Takeda, M., Ejima, W., Kawasaki, Y., Umezu, T., Yamada, M., Koizumi, J., Mashima, T., and Katahira, M.
  • 雑誌名: Internat. J. Biol. Macro mol. 巻: 48 ページ: 256-262
  • DOI: doi:10.1016/j.ijbiomac.2010.11.009
  • 査読あり
• [雑誌論文] Solution structures of the trihelix DNA-binding domains of the wild-type and a phosphomimetic mutant of Arabidopsis GT-1 (2010)
  • 著者名/発表者名: Nagata, T., Niyada, E., Fujimoto, N., Nagasaki, Y., Noto, K., Miyanoiri, Y., Murata, J., Hiratsuka, K. and Katahira, M.
  • 雑誌名: Proteins 巻: 78 ページ: 3033-3047
  • DOI: DOI:10.1002/prot.22827
  • 査読あり
• [雑誌論文] Solubilization and structural determination of a glycoconjugate which isassembled into the sheath of Leptothrixcholodnii (2010)
  • 著者名/発表者名: Takeda, M., Kondo, K., Yamada, M., Koizumi, J., Mashima, T., Matsugami, A. and Katahira, M.
  • 雑誌名: Int. J. Biol. Macro mol 巻: 46 ページ: 206-211
  • DOI: doi:10.1016/j.ijbiomac.2009.12.006
  • 査読あり
• [雑誌論文] Structure, interaction, and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G (2009)
  • 著者名/発表者名: Furukawa, A., Nagata, T., Matsugami, A., Habu, Y., Sugiyama, R., Hayashi, F., Yokoyama, S., Takaku, H. and Katahira, M.
  • 雑誌名: EMBO J. 巻: 28 ページ: 440-451
  • DOI: doi:10.1038/emboj.2008.290
  • 査読あり
• [雑誌論文] Uniquequadruplex structure and interaction of anRNA aptamer against bovine prion protein (2009)
  • 著者名/発表者名: Mashima, T., Matsugami, A., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 雑誌名: Nucleic Acids Res. 巻: 37 ページ: 6249-6258
  • DOI: doi:10.1093/nar/gkp647
  • 査読あり
• [雑誌論文] The orientation of the ends of G-quadruplex structures investigated using end-extended oligonucleotides (2009)
  • 著者名/発表者名: Sannohe, Y., Sato, K., Matsugami, A., Shinohara, K., Mashimo, T., Katahira, M. and Sugiyama, H.
  • 雑誌名: Bioorg. Medici. Chem. 巻: 17 ページ: 1870-1875
  • DOI: doi:10.1016/j.bmc.2009.01.051
  • 査読あり
• [雑誌論文] Structural studies of an RNA aptamer containing GGArepeats under ionic conditions using microchip electrophoresis (2009)
  • 著者名/発表者名: Nishikawa, F., Murakami, K., Matsugami, A., Katahira, M. and Nishikawa, S.
  • 雑誌名: Oligonucleotides 巻: 19 ページ: 179-190
  • DOI: doi:10.1089/oli.2008.0167
  • 査読あり
• [学会発表] Sliding-direction-dependent activity of anti-HIV enzyme, and structural basis of anti-prion activity of RNA aptamer (2012)
  • 著者名/発表者名: Furukawa, A., Mashima, T., Sugase, K., Fujiwara, H., Nagata, T., Morishita, R., Ryo, A., Nishikawa, F., Nishikawa, S., Kamatari, Y., Kuwata, K. and Katahira, M.
  • 学会等名: Korea-Japan Bilateral NMR Symposium
  • 発表場所: Sapporo
  • 年月日: 2012-03-16
• [学会発表] Towards evaluation of wood cell wall structures and those biodegradation using solution NMR (2012)
  • 著者名/発表者名: Nishimura, H., Kozawa, Y., Okamura, H., Watanabe, T. and Katahira, M.
  • 学会等名: Korea-Japan Bilateral NMR Symposium
  • 発表場所: Sapporo
  • 年月日: 2012-03-16
• [学会発表] Recognition of prion protein by the RNA aptamer (2012)
  • 著者名/発表者名: Mashima, T., Fujiwara, H., Nishikawa, F., Saimura, M., Kamatari, Y., Kuwata, K., Imamura, M., Yokoyama, T., Nishikawa, S. and Katahira, M.
  • 学会等名: Korea-Japan Bilateral NMR Symposium
  • 発表場所: Sapporo
  • 年月日: 2012-03-16
• [学会発表] Base-deamination rate dependent on the direction of sliding of an enzyme along DNA as revealed by numerical analysis of NMR data, and wood biomass studied by solution NMR (2011)
  • 著者名/発表者名: Nishimura, H., Furukawa, A., Okamura, H., Kozawa, Y., Morishita, R., Ryo, A., Sugase, K., Watanabe, T. and Katahira, M.
  • 学会等名: The International Symposium on Nuclear Magnetic Resonance 2011
  • 発表場所: Yokohama
  • 年月日: 20111115-18
• [学会発表] r(GGA) 4 chimeric ribozyme switches its activity in response to K+ via quadruplex formation (2011)
  • 著者名/発表者名: Nagata, T., Sakurai, Y., Mashima, T. and Katahira, M.
  • 学会等名: The 38th International Symposium on Nucleic Acids Chemistry
  • 発表場所: Sapporo
  • 年月日: 20111109-11
• [学会発表] Elucidation of functions on APOBEC3DE and APOBEC3F based on structure-oriented analysis (2011)
  • 著者名/発表者名: Iwaoka, R., Furukawa, A., Okamura, H. and Katahira, M.
  • 学会等名: 3^<rd> G-COE International Symposium Zero Carbon Energy 2011
  • 発表場所: 水原
  • 年月日: 20110818-19
• [学会発表] Structural basis of the high affinity of the RNA aptamer against prion protein (2011)
  • 著者名/発表者名: Mashima, T., Fujiwara, H., Koshida, T., Saimura, M., Imamura, M., Yokoyama, T., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: The 16th annual meeting of the RNA society
  • 発表場所: Kyoto
  • 年月日: 20110614-18
• [学会発表] Structure and interaction of an RNA aptamer with potential therapeutic use (2010)
  • 著者名/発表者名: Mashima, T., Matsugami, A., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: The International Chemical Congress of Pacific Basin Societies
  • 発表場所: Hawaii
  • 年月日: 20101215-20
• [学会発表] Unique quadruplex structure and interaction of r(GGAGGAGGAGGA) with protein (2010)
  • 著者名/発表者名: Mashima, T., Matsugami, A., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: The International Chemical Congress of Pacific Basin Societies
  • 発表場所: Hawaii
  • 年月日: 20101215-20
• [学会発表] Structural aspects of the fluorescence intensity changes of the ATP-binding ribonucleopeptide sensor (2010)
  • 著者名/発表者名: Yoshioka, K., Daidai, M., Katahira, M. and Watanabe, T.
  • 学会等名: The International Chemical Congress of Pacific Basin Societies
  • 発表場所: Hawaii
  • 年月日: 20101215-20
• [学会発表] Structure and interaction of RNA aptamer againstprion protein in complex with the partial binding peptide (2010)
  • 著者名/発表者名: Mashima, T., Koshida, T., Saimura, M., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: The 37th International Symposium on Nucleic Acids Chemistry 2010
  • 発表場所: Yokohama
  • 年月日: 20101110-12
• [学会発表] Structure and interaction of RNA aptamer against prion protein in complex with the partial binding peptide (2010)
  • 著者名/発表者名: Nagata, T., Niyada, E., Fujimoto, N., Nagasaki, Y., Noto, K., Miyanoiri, Y., Murata, J., Hiratsuka, K. and Katahira, M.
  • 学会等名: The 37th International Symposium on Nucleic Acids Chemistry 2010
  • 発表場所: Yokohama
  • 年月日: 20101110-12
• [学会発表] A mechanism for a increase in DNA-binding affinity of the trihelix DNA-binding domain via its phosphrylation (2010)
  • 著者名/発表者名: Nakano, S., Mashima, T., Tainaka, K., Katahira, M. and Morii, T.
  • 学会等名: The 37th International Symposium on Nucleic Acids Chemistry 2010
  • 発表場所: Yokohama
  • 年月日: 20101110-12
• [学会発表] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure and interaction of the RNA aptamer against prion protein (2010)
  • 著者名/発表者名: Furukawa, A., Mashima, T., Nagata, T., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: The 10th KIAS Conference on Protein Structure and Function
  • 発表場所: Seoul
  • 年月日: 20100930-1002
• [学会発表] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure of the RNA aptamer against prion protein (2010)
  • 著者名/発表者名: Mashima, T., Furukawa, A., Nagata, T., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: XXIV International Conference on Magnetic Resonance in Biological Systems
  • 発表場所: Cairns
  • 年月日: 20100822-27
• [学会発表] The real-time monitoring of the enzymatic reaction of an anti-HIV factor APOBEC3G (2010)
  • 著者名/発表者名: Furukawa, A., Nagata, T., Morishita, R., Iwaoka, R. and Katahira, M.
  • 学会等名: XXIV International Conference on Magnetic Resonance in Biological Systems
  • 発表場所: Cairns
  • 年月日: 20100822-27
• [学会発表] The analysis of the mechanism of an enzyme reaction toward the development of new energy systems (2010)
  • 著者名/発表者名: Iwaoka, R., Furukawa, A. and Katahira, M.
  • 学会等名: The 2nd International Symposium of Kyoto University Global COE Program Zero Carbon Energy Kyoto 2010
  • 発表場所: Kyoto
  • 年月日: 20100819-20
• [学会発表] Real-time monitoring of the cytidine deamination along single-stranded DNA by an anti-HIV factor (2010)
  • 著者名/発表者名: Furukawa, A., Mashima, T., Matsugami, A., Nagata. T., Sugiyama, R., Takaku, H., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: The International Symposium on Nuclear Magnetic Resonance 2011
  • 発表場所: Seoul
  • 年月日: 20100517-19
• [学会発表] The real-time monitoring of the enzymatic reaction of an anti-HIV factor APOBEC3G (2010)
  • 著者名/発表者名: Furukawa, A., Nagata, T., Morishita, R., Iwaoka, R. and Katahira, M.
  • 学会等名: Korea-Japan Bilateral NMR Symposium
  • 年月日: 20100000
• [学会発表] Real-time monitoring of the enzymatic reaction of APOPBEC3G possessing anti-HIV activity, and the structure of the RNA aptamer against prion (2009)
  • 著者名/発表者名: Furukawa, A., Mashima, T., Nagata, T., Takaku, H., Matsugami, A., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: The 3rd Asia-Pacific NMR Symposium
  • 発表場所: Cheju
  • 年月日: 20091115-18
• [学会発表] Structural analysis of ribonucleopeptide aptamer against ATP (2009)
  • 著者名/発表者名: Mashima, T., Matsugami, A., Nakano, S., Inoue, M., Fukuda, M., Morii, T. and Katahira, M.
  • 学会等名: The 6^<th> International Symposium on Nucleic Acids Chemistry
  • 発表場所: Gifu
  • 年月日: 20091104-06
• [学会発表] Structure and real-time monitoring of the enzymatic reaction of APOBEC3G which is involved in anti-HIV activity (2009)
  • 著者名/発表者名: Furukawa, A., Nagata, T., Matsugami, A., Habu, Y., Sugiyama, R., Hayashi, F., Kobayashi, N., Yokoyama, S., Takaku, H. and Katahira, M.
  • 学会等名: The 6th International Symposium on Nucleic Acids Chemistry
  • 発表場所: Gifu
  • 年月日: 20091104-06
• [学会発表] Structural aspects for the function of ATP-binding ribonucleopeptide receptors (2009)
  • 著者名/発表者名: Nakano, S., Fukuda, M., Mashima, T., Katahira, M. and Morii, T.
  • 学会等名: The 6^<th> International Symposium on Nucleic Acids Chemistry
  • 発表場所: Gifu
  • 年月日: 20091104-06
• [学会発表] Unique quadruplex structure and interaction of the RNA aptamer against bovine prion protein (2009)
  • 著者名/発表者名: Mashima, T., Matsugami, A., Nishikawa, F., Nishikawa, S. and Katahira, M.
  • 学会等名: Joint Symposium of the 5^<th> annual Meeting of the Oligonucleotide Therapeutics Society and the 19^<th> Antisense Symposium
  • 発表場所: Fukuoka
  • 年月日: 20091104-06
• [学会発表] Structure, interaction and real-time monitoring of the enzymatic reaction of APOBEC3G which possesses anti-HIV activity (2009)
  • 著者名/発表者名: Furukawa, A., Nagata, T., Sugiyama, R., Takaku, H. and Katahira, M.
  • 学会等名: The 3rd Asia-Pacific NMR Symposium
  • 発表場所: Cheju
  • 年月日: 20091025-28
• [図書] Encyclopedia of Biophysics,"Introduction to Nucleic Acids NMR" (2012)
  • 著者名/発表者名: Katahira, M. and Mashima, T.
  • 出版者: Springer
• [図書] 日本化学会編・CSJカレントレビュー"核酸化学のニュートレンド-DNA・RNAの新たな可能性を開く""論文にみる最重要概念と革新実験データ" (2011)
  • 著者名/発表者名: 片平正人
  • 総ページ数: 36-40
  • 出版者: 化学同人
• [備考]
  • URL: http://www.iae.kyoto-u.ac.jp/bio/a-13_j.html
• [産業財産権] Nucleic Acid-Enzyme Complex (2011)
  • 発明者名: 片平正人
  • 権利者名: 横浜国立大学長飯田嘉宏
  • 産業財産権番号: 特許、7910721
  • 取得年月日: 2011-03-10
  • 外国