Dynamics of Nucleosome Assembly in Solution Revealed by X-ray and Neutron Scattering

• Project/Area Number: 25291037
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biophysics
• Research Institution: Yokohama City University
• Principal Investigator: Sato Mamoru 横浜市立大学, 生命医科学研究科, 教授 (60170784)
• Co-Investigator(Kenkyū-buntansha): ODA Takashi 横浜市立大学, 大学院生命医科学研究科, 特任助教 (00573164)
• Co-Investigator(Renkei-kenkyūsha): KURUMIZAKA Hitoshi 早稲田大学, 大学院先進理工学研究科, 教授 (80300870)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 溶液散乱 / 小角散乱 / クロマチン / ヌクレオソーム / セントロメア / 分子動力学計算 / 粗視化モデル

Outline of Final Research Achievements

Solution X-ray and neutron scattering analyses have showed that both ends of double stranded DNA in H2A.B nucleosome are peeled off from the histone octamer and is exposed to the solvent. This facilitates the chromatin takes a looser conformation than H2A nucleosome. Also, solution X-ray scattering analysis indicates that conformation of higher-order nucleosome complex, H3-(CENP-A)-H3 tri-nucleosome is more opened than that of H3-H3-H3 tri-nucleosome. Furthermore, MD-SAXS analysis (solution X-ray scattering analysis combined with molecular dynamics calculation) using a coarse grained model as a tri-nucleosome has analyzed the dynamical structure of the chromatin in centromere and non-centromere regions at atomic resolution and elucidated the functional significance of the chromatin containing CENP-A nucleosome in the centromere.

Research Products

• [Journal Article] Extended string-like binding of the phosphorylated HP1α N-terminal tail to the lysine 9-methylated histone H3 tail. (2016)
  • Author(s): Shimojo H, Kawaguchi A, Oda T, Hashiguchi N, Omori S, Moritsugu K, Kidera A, Hiragami-Hamada K, Nakayama J, Sato M, Nishimura Y.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 22527-22527
  • DOI: 10.1038/srep22527
  • Peer Reviewed / Open Access
• [Journal Article] Molecular basis for SMC rod formation and its dissolution upon DNA binding (2015)
  • Author(s): Y. Soh, F. Bürmann, H. Shin, T. Oda, K. S. Jin, C. P. Toseland, C. Kim, H. Lee, S. J. Kim, M. Kong, M. Durand-Diebold, Y. Kim, H. M. Kim, N. K. Lee, M. Sato, B. Oh, S. Gruber
  • Journal Title: Mol. Cell Volume: 57 Issue: 2 Pages: 290-303
  • DOI: 10.1016/j.molcel.2014.11.023
  • Peer Reviewed / Open Access
• [Journal Article] A magnetic anti-cancer compound for magnet-guided delivery and magnetic resonance imaging. (2015)
  • Author(s): Eguchi H, Umemura M, Kurotani R, Fukumura H, Sato I, Kim J-H, Hoshino Y, Lee J, Amemiya N, Sato M, Hirata K, Sigh DJ, Masuda T, Yamamoto M, Urano T, Yoshida K, Tanigaki K, Yamamoto M, Sato M, Inoue S, Aoki I and Ishikawa Y.
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 9194-9194
  • DOI: 10.1038/srep09194
  • Peer Reviewed / Open Access
• [Journal Article] Charge-neutralization effect of the tail regions on the histone H2A/H2B dimer structure. (2015)
  • Author(s): Saikusa, K., Shimoyama, S., Asano, Y., Nagadoi, A., Sato, M., Kurumizaka, H., Nishimura, Y., and Akashi, S.
  • Journal Title: Protein Science Volume: - Issue: 8 Pages: 20-27
  • DOI: 10.1002/pro.2673
  • Peer Reviewed / Open Access
• [Journal Article] A novel 3' splice site recognition by the two zinc fingers in the U2AF small subunit. (2015)
  • Author(s): Yoshida H, Park S-Y, Oda T, Akiyoshi T, Sato M, Shirouzu M, Tsuda K, Kuwasako K, Unzai S, Muto Y, Urano T, Obayashi E.
  • Journal Title: Genes Dev. Volume: 29 Issue: 15 Pages: 1649-1660
  • DOI: 10.1101/gad.267104.115
  • Peer Reviewed / Open Access
• [Journal Article] Structure of a novel DNA-binding domain of helicase-like transcription factor (HLTF) and its functional implication in DNA damage tolerance. (2015)
  • Author(s): Hishiki, A., Hara, K., Ikegaya, Y., Yokoyama, H., Shimizu, T., Sato, M., Hashimoto, H.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 21 Pages: 13215-13223
  • DOI: 10.1074/jbc.m115.643643
  • Peer Reviewed / Open Access
• [Journal Article] Distinct features of the histone core structure in nucleosomes containing the histone H2A.B variant. (2014)
  • Author(s): Sugiyama M, Arimura Y, Shirayama K, Fujita R, Oba Y, Sato N, Inoue R, Oda T, Sato M, Heenan RK, Kurumizaka H.
  • Journal Title: Biophys J. Volume: 106 Issue: 10 Pages: 2206-2213
  • DOI: 10.1016/j.bpj.2014.04.007
  • Peer Reviewed / Open Access
• [Journal Article] A structure-based model of substrate discrimination by a non-canonical PDZ tandem in the intramembrane-cleaving protease RseP. (2014)
  • Author(s): 檜作 洋平, 小田 隆, 田畑 早苗, 川上-田村 恵子, 大井 里香, 佐藤 衛, 高木 淳一, 秋山 芳展, 禾 晃和
  • Journal Title: Structure Volume: 22 Issue: 2 Pages: 326-336
  • DOI: 10.1016/j.str.2013.12.003
  • Peer Reviewed
• [Journal Article] Crystal structure of Cex1p reveals the mechanism of tRNA trafficking between nucleus and cytoplasm (2013)
  • Author(s): K. Nozawa, R. Ishitani, T. Yoshihisa, M. Sato, F. Arisaka, S. Kanamaru, N. Dohmae, D. Mangroo, B. Senger, H. D. Becker and O. Nureki
  • Journal Title: Nucleic Acids Research Volume: 41 Issue: 6 Pages: 3901-3914
  • DOI: 10.1093/nar/gkt010
  • Peer Reviewed
• [Journal Article] Report of the wwPDB Small-Angle Scattering Task Force : Data Requirements for Biomolecular Modeling and the PDB (2013)
  • Author(s): J.Trewhella, W.A.Hendrickson, G.J.Kleywegt, A.Sali, M.Sato, T.Schwede, D.I.Svergun, J.A.Tainer, J.Westbrook, and H.M.Berman
  • Journal Title: Structure Volume: 21 Issue: 6 Pages: 875-881
  • DOI: 10.1016/j.str.2013.04.020
  • Peer Reviewed
• [Journal Article] Structural basis of a nucleosome containing histone H2A. B/H2A. Bbd that transiently associates with reorganized chromatin. (2013)
  • Author(s): Arimura Y., Kimura H., Oda T., Sato K., Osakabe A., Tachiwana H., Sato Y., Kinugasa Y., Ikura T., Sugiyama M., Sato M., Kurumizaka H.
  • Journal Title: Sci Rep. Volume: 3 Issue: 1 Pages: 3510-3510
  • DOI: 10.1038/srep03510
  • Peer Reviewed / Open Access
• [Presentation] MD-SAXSによるタンパク質のゆらぎ解析 (2015)
  • Author(s): 池口満徳, 小甲裕一, 佐藤 衛
  • Organizer: 日本結晶学会平成27年度年会
  • Place of Presentation: 大阪府立大学
  • Year and Date: 2015-10-18
  • Invited
• [Presentation] Coarse-Grained MD-SAXS method and application to nucleosomes (2015)
  • Author(s): Y. Kokabu, T. Oda, M. Sugiyama, H. Kurumizaka, M. Sato, M. Ikeguchi
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 金沢大学
  • Year and Date: 2015-09-13
• [Presentation] タンパク質の天然変性領域を標的にした創薬 (2015)
  • Author(s): 佐藤 衛
  • Organizer: 翻訳後修飾プロテオミクス医療研究拠点の形成―平成26年度諮問委員会
  • Place of Presentation: 横浜市立大学附属病院
  • Year and Date: 2015-03-10
  • Invited
• [Presentation] Ｘ線溶液散乱法を中心にした軟らかなタンパク質の相関構造解析 (2014)
  • Author(s): 佐藤 衛
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪大学蛋白質研究所
  • Year and Date: 2014-12-04 – 2014-12-05
  • Invited
• [Presentation] 赤痢菌IpaBによるMad2L2の機能阻害複合体の結晶学的研究 (2014)
  • Author(s): 片川裕理、原 幸大、花岡祐樹、菊池壮太郎、横山英志、金 文秀、笹川千尋、佐藤 衛、橋本 博
  • Organizer: 平成26年度日本結晶学会年会
  • Place of Presentation: 東京大学農学部
  • Year and Date: 2014-11-01 – 2014-11-03
• [Presentation] Ｘ線溶液散乱を中心にした相関構造解析－揺らぎの大きい軟らかなタンパク質の構造解析を目指して (2014)
  • Author(s): 佐藤 衛
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] 細胞表層ストレス応答制御に関わる膜内切断プロテアーゼRsePのタンデムPDZドメインによる切断基質選別機構の解析 (2014)
  • Author(s): 檜作 洋平, 小田 隆, 田畑 早苗, 川上-田村 恵子, 大井里香, 佐藤 衛, 高木 淳一, 禾 晃和, 秋山 芳展
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Structural dynamics of tri-nucleosome studied by combination of coarse grained molecular simulation and SAXS (2014)
  • Author(s): Yusuke Takagi, Yuichi Kokabu, Takashi Oda, Hiroaki Tachiwana, Hiroo Kenzaki, Hitoshi Kurumizaka, Mamoru Sato, Mitsunori Ikeguchi, Shoji Takada
  • Organizer: 日本生物物理学会第52回年会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Structural and mutational analysis of a PDZ tandem of intramembrane cleaving protease RseP (2014)
  • Author(s): Terukazu Nogi, Yohei Hizukuri, Sanae Tabata, Keiko Tamura-Kawakami, Takashi Oda, Mamoru Sato, Junichi Takagi, Yoshinori Akiyama
  • Organizer: XXIII Congress of the International Union of Crystallography
  • Place of Presentation: Palais des congress de Montreal, Quebec, Canada
  • Year and Date: 2014-08-05 – 2014-08-12
• [Presentation] DNA架橋損傷修復に関わる天然変性タンパク質Hefの構造研究 (2014)
  • Author(s): 小田 隆、小林裕也、舘岡太郎、宮城泰城、石黒あかり、有田恭平、禾 晃和、石野良純、杉山正明、佐藤 衛
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: ワークピア横浜（横浜）
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] SAXS & MD Simulation to Investigate Protein Flexibility in Solution (2013)
  • Author(s): Mamoru Sato
  • Organizer: International Symposium on Diffraction Structural Biology (ISDSB2013)
  • Place of Presentation: Nagoya Trade & Industry Center
  • Invited
• [Presentation] 天然変性領域をターゲットにした抗体医薬の創成を目指して (2013)
  • Author(s): 佐藤 衛
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: とりぎん文化会館（鳥取）
  • Invited
• [Presentation] REV7-REV3複合体構造から示唆されるREV7/Mad2L2と赤痢菌タンパク質IpaBとの相互作用 (2013)
  • Author(s): 菊池 壮太郎、原 幸大、清水 敏之、佐藤 衛、橋本 博
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: とりぎん文化会館（鳥取）
• [Presentation] Protein Dynamics Investigated by SAXS and MD Simulation (2013)
  • Author(s): Mamoru Sato
  • Organizer: International Conference on Structural Genomics-Structural Life Science-(ICSG2013-SLS)
  • Place of Presentation: Keio Plaza Hotel Sapporo in Sapporo
  • Invited
• [Presentation] Structural study on REV7, the adaptor protein coordinating REV1 and REV3 polymerase in ttanslesion DNA synthesis (2013)
  • Author(s): Sotaro Kikuchi, Kodai Hara, Toshiyuki Shimizu, Mamoru Sato, Hiroshi Hashimoto
  • Organizer: International Conference on Structural Genomics-Structural Life Science-(ICSG2013-SLS)
  • Place of Presentation: Keio Plaza Hotel Sapporo in Sapporo
• [Presentation] Structural analysis of the PDZ tandem fragment of the bacterial intramembrane-cleaving protease RseP (2013)
  • Author(s): Terukazu Nogi, Yohei Hizukuri, Takashi Oda, Sanae Tabata, Keiko Tamura-Kawakami, Mamoru Sato, Junichi Takagi, Yoshinori Akiyama
  • Organizer: International Conference on Structural Genomics-Structural Life Science-(ICSG2013-SLS)
  • Place of Presentation: Keio Plaza Hotel Sapporo in Sapporo
• [Presentation] 将来光源を用いた新しいタンパク質の構造・機能研究 (2013)
  • Author(s): 佐藤 衛
  • Organizer: 第31回関西界面科学セミナー
  • Place of Presentation: SPring-8 普及棟
  • Invited
• [Presentation] 大腸菌膜内切断プロテアーゼRsePの基質認識におけるPDZドメインの役割 (2013)
  • Author(s): 檜作 洋平, 禾 晃和, 小田 隆, 田畑 早苗, 川上-田村 恵子, 佐藤 衛, 高木 淳一, 秋山 芳展
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ヒトヒストンバリアントH2A.Bの解析 (2013)
  • Author(s): 有村泰宏、小田 隆、佐藤浩一、藤田理紗、松本亮平、田口裕之、堀越直樹、越阪部晃永、立和名博昭、杉山正明、佐藤 衛、木村 宏、胡桃坂仁志
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 天然変性タンパク質（領域）をターゲットにした創薬 (2013)
  • Author(s): 佐藤 衛
  • Organizer: 静岡県立大学薬学部第238回月例薬学セミナー
  • Place of Presentation: 静岡県立大学小講堂
  • Invited
• [Presentation] 表層ストレス応答を制御する腸内切断プロテアーゼRsePのタンデムPDZドメインによる基質選別機構 (2013)
  • Author(s): Yohei Hizukuri, Takashi Oda, Sanae Tabata, Tamura-Kawakami Keiko, Mamoru Sato, Junichi Takagi, Terukazu Nogi, Yoshimori Akiyama
  • Organizer: 日本生物物理学会第51回年会
  • Place of Presentation: 国立京都国際会館
• [Presentation] N-terminal phosphorylated tail of HP1α behaves like an extended hard acidic string to promote the binding to methylated histone H3K9 tail (2013)
  • Author(s): Mayumi Kawaguchi, Hideaki Shimojo, Kyoko Hamada, Jun-ichi Nakayama, Takashi Oda, Mamoru Sato, Yoshifumi Nishimura
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 低エミッタンス高輝度光源を用いたタンパク質の新しい構造解析法の提案 (2013)
  • Author(s): 佐藤 衛
  • Organizer: 第３世代中型高輝度放射光源（SLiT-J）の実現に向けて―先端学術研究と産業技術支援―
  • Place of Presentation: 東北大学金属材料研究所
  • Invited
• [Patent(Industrial Property Rights)] 新規抗PAD4抗体 (2016)
  • Inventor(s): 佐藤 衛、山田道之、金澤 智、豊浦雅義、庄屋雄二、斉藤憲二
  • Industrial Property Rights Holder: 佐藤 衛、山田道之、金澤 智、豊浦雅義、庄屋雄二、斉藤憲二
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-03-07
  • Overseas