Structural Basis for diverse functions of the Rad18 protein

• Project/Area Number: 19390012
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: YAMAGATA Yuriko Kumamoto University, 大学院・医学薬学研究部, 教授 (40183678)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2007: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
• Keywords: 生物物理化学 / 構造生物学 / DNA修復 / 蛋白質複合体 / 蛋白質結晶化 / X線結晶構造解析 / タンパク質-DNA複合体

Research Abstract

様々なDNAの損傷に対して生物はDNAを修復する様々な仕組みをもっている。そのようなDNAの修復に重要なRad18の働く仕組みをRad18相互作用するタンパク質やDNAとの複合体の結晶化を行いRad18/Rad6複合体の結晶を得た。さらにRad18のSAPドメインが複製フォーク様DNAとの結合に重要であることをドメインの構造モデルを構築することによって説明した。

Research Products

• [Journal Article] Crystallization and preliminary Xray analysis of the tumor necrosis factor α-tumor necrosis factor receptor type 2 complex. (2009)
  • Author(s): Mukai Y, Nakamura T, Yoshioka Y, Tsunoda S, Kamada H, Nakagawa S, Yamagata Y, and Tsutsumi Y.
  • Journal Title: Acta Cryst. F65 Pages: 295-298
  • Peer Reviewed
• [Journal Article] Structure-function relationship of tumor necrosis factor (TNF) and its receptor interaction based on 3D structural analysis of a fully active TNFR1-selective TNF mutant. (2009)
  • Author(s): Mukai, Y., et al., and Yamagata, Y., Tsutsumi Y., 他9名
  • Journal Title: J. Mol. Biol. 385 Pages: 1221-1229
  • Peer Reviewed
• [Journal Article] structure-function relationship of tumor necrosis factor (TNF)and its receptor interaction based an 3D structural analysis of a My active TNFRl-selective TNF mutant (2009)
  • Author(s): Mukai, Y., et al.
  • Journal Title: Journal of Molecular Biology 381 Pages: 1221-1229
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary Xray analysis of the tumor necrosis factor α-tumor necrosis factor receptor type 2 complex. (2009)
  • Author(s): Mukai, Y., et al.
  • Journal Title: Acta Cryst. F65 Pages: 295-298
  • Peer Reviewed
• [Journal Article] Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RADB protein triggers its recruitment to stalled replication forks. (2008)
  • Author(s): Tsuji, Y., Watanabe, K., Araki, K., Shinohara, M., Yamagata, Y., Tsurimoto, T., Hanaoka, F., Yamamura, K., Yamaizumi, M., and Tateishi
  • Journal Title: S. Genes to Cells 13 Pages: 343-354
  • Peer Reviewed
• [Journal Article] Preparation, crystallization and preliminary X-ray diffraction analysis of the DNA binding domain of the Ets transcription factor in complex with target DNA (2008)
  • Author(s): Suwa, Y., Nakamura, T., Toma, S., Ikemizu, S., Kai H., and Yamagata Y.
  • Journal Title: Acta Cryst. F64 Pages: 171-174
  • Peer Reviewed
• [Journal Article] Creation and X-ray structure analysis of the tumor necrosis factor receptor-1 selective mutant of a TNF.antagonist. (2008)
  • Author(s): Shibata, H., et al., and Yamagata, Y., Tsunoda, S., Kamada, H., Tsutsumi Y., 他22名
  • Journal Title: J. Biol. Chem. 283 Pages: 998-1007
  • Peer Reviewed
• [Journal Article] Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RADB protein triggers its recruitment to stalled replication forks (2008)
  • Author(s): Tsuji, Y., et al.
  • Journal Title: Genes to Cells 13 Pages: 343-354
  • Peer Reviewed
• [Journal Article] Preparation,crystallization and preliminary X-ray diffraction analysis of the DNA binding domain of the Ets transcription factor in complex with target DNA. (2008)
  • Author(s): Suwa Y., et. al.
  • Journal Title: Acta Cryst. F64 Pages: 171-174
  • Peer Reviewed
• [Journal Article] Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RADB protein triggers its recruitment to stalled replication forks (2008)
  • Author(s): Tsuji, Y., et. al.
  • Journal Title: Genes to Cells 13 Pages: 343-354
  • Peer Reviewed
• [Journal Article] Crystal structure of the IL-15-IL-15Rα complex, a cytokine-receptor unit presented in trans. (2007)
  • Author(s): Chirifu, M., Hayashi, C., Nakamura, T., Toma, S., Shuto, T., Kai, H., Yamagata, Y., Davis S.J., and Ikemizu, S.
  • Journal Title: Nature Immunol 8 Pages: 1001-1007
  • Peer Reviewed
• [Journal Article] Crystallographic Investigation of the Inhibition Mode of a VIM-2 Metallo-・-lactamase from Pseudomonas aeruginosa by a Mercaptocarboxylate Inhibitor. (2007)
  • Author(s): Yamaguchi, Y., Jin, W., Matsunaga, K., Ikemizu, S., Yamagata, Y., Wachino, J., Shibata, N., Arakawa, Y., and Kurosaki H.
  • Journal Title: J. Med. Chem. 50 Pages: 6647-6653
  • Peer Reviewed
• [Journal Article] アルツハイマー病治療薬塩酸ドネペジルによるアセチルコリンエステラーゼの阻害機構 (2007)
  • Author(s): 中村照也、山縣ゆり子
  • Journal Title: 医薬ジャーナル 43, No.5 Pages: 5-14
• [Journal Article] Crystal structure of the IL-15-1L-15Rα complex,a cytokine-receptor unit presented in trans (2007)
  • Author(s): Chirifu M., et. al.
  • Journal Title: Nature Immunol. 8 Pages: 1001-1007
  • Peer Reviewed
• [Presentation] 機能未知であるヒト一回膜貫通型タンパク質のC末ドメインの立体構造決定 (2009)
  • Author(s): 山縣ゆり子
  • Organizer: 日本薬学会第129回年会
  • Place of Presentation: 京都
• [Presentation] hMTH1による8-oxo-dGTPの基質認識と加水分解反応機構の構造学的基盤 (2009)
  • Author(s): 稲里みゆき
  • Organizer: 次世代を担う若手のためのフィジカル・ファーマフォーラム(PPF2009)
  • Place of Presentation: 高槻
• [Presentation] 中性子回折実験のための大型結晶作成の試み (2009)
  • Author(s): 山縣ゆり子
  • Organizer: タンパク質結晶育成研究会
  • Place of Presentation: 東海村
• [Presentation] 蛋白質の立体構造から熱安定化機構と分子間相互作用を探る (2008)
  • Author(s): 山縣ゆり子
  • Organizer: 財団法人化学及血清療法研究所KIKUCHIバイオセミナー
  • Place of Presentation: 熊本
  • Year and Date: 2008-05-16
• [Presentation] 変異原ヌクレオチド分解酵素の反応機構解明 (2008)
  • Author(s): 山縣ゆり子
  • Organizer: 第32回蛋白質と酵素の構造と機能に関する九州シンポジウム
  • Place of Presentation: 阿蘇
• [Presentation] Structural insights into the substrate recognition and hydrolysis reaction mechanisms of 8-oxo-dGDPase. (2008)
  • Author(s): Takao Arimori
  • Organizer: IUCr
  • Place of Presentation: Osaka
• [Presentation] High resolution X-ray diffraction study of the hMTH1 mutant (2008)
  • Author(s): Teruya Nakamura
  • Organizer: IUCr
  • Place of Presentation: Osaka
• [Presentation] Structural basis for transcriptional regulation mechanisms by the transcription factor Ets2. (2008)
  • Author(s): Yoshiaki Suwa
  • Organizer: IUCr
  • Place of Presentation: Osaka
• [Presentation] 8-oxo-dGDP加水分解酵素における基質認識機構および反応機構の構造学的基盤 (2008)
  • Author(s): 有森貴夫(ポスター賞受賞)
  • Organizer: 第8回日本蛋白質科学会年会
  • Place of Presentation: 東京
• [Presentation] ヒトMTH1蛋白質の機能解明に必須の高分解能X線結晶構造解析 (2008)
  • Author(s): 山縣ゆり子
  • Organizer: 第21回日本放射光学会年会・放射光科学合同シンポジウム
  • Place of Presentation: 草津
• [Presentation] Structure-function relationships of enzymes for oxidative nucleotide processing (2007)
  • Author(s): Yuriko Yamagata
  • Organizer: 2007 Frontier Research Symposium on Genome Stability in Control of Diseases and Aging at Fukuoka Dental College
  • Place of Presentation: Fukuoka
  • Year and Date: 2007-10-29
• [Presentation] DNA 修復関連酵素による核酸塩基の正常と異常の識別に関する構造生物学的研究 (2007)
  • Author(s): 山縣 ゆり子
  • Organizer: 変異機構研究会・第20回夏の学校
  • Place of Presentation: 愛知
  • Year and Date: 2007-07-28
• [Presentation] ゲノムの酸化損傷を抑制するタンパク質の構造生物学的研究 (2007)
  • Author(s): 山縣ゆり子
  • Organizer: 独立行政法人医薬基盤研究所セミナー
  • Place of Presentation: 大阪
  • Year and Date: 2007-05-18
• [Presentation] hMTH1による8-oxo-dATPの認識機構 (2007)
  • Author(s): 山縣ゆり子
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: 横浜
• [Presentation] STRUCTURE-BASED DESIGN OF INHIBITORS OF HUMAN MTH1 PROTEIN I (2007)
  • Author(s): Yuriko Yamagata
  • Organizer: The 8th Conference of the Asian Crystallographic Association
  • Place of Presentation: Taipei
• [Presentation] DNA修復関連酵素による核酸塩基の正常と異常の識別に関する構造生物学的研究 (2007)
  • Author(s): 山縣ゆり子
  • Organizer: 変異機構研究会・第20回夏の学校
  • Place of Presentation: 名古屋
• [Book] 2章X線結晶構造解析法の展開, 薬学分析科学の最前線 (2009)
  • Author(s): 中村照也、山縣ゆり子(日本薬学会物理系薬学部・分析化学担当教員会議編)
  • Publisher: (株)じほう