Structural study of the genome maintenance mechanism by the Werner syndrome protein WRN

• Project/Area Number: 19770084
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: KITANO Ken Nara Institute of Science and Technology, 情報科学研究科, 助教 (40346309)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: タンパク質 / X線結晶構造解析 / ウェルナー症候群 / ブルーム症候群 / 早老症 / DNAヘリカーゼ / X線 / 結晶構造解析 / ゲノム / 老化 / ヘリカーゼ

Research Abstract

ウェルナー症候群は,若い年齢で老化が急速に進行する早老症の病気のひとつである。本研究ではその原因タンパク質 WRNヘリカーゼの結晶を作成し,大型放射光施設 SPring-8を使ったX線構造解析の研究を進めた。この結果,WRN RQC(RecQ C-terminal)ドメインとDNAの複合体構造を初めて決定することに成功した。WRNは尖ったヘアピン構造を“DNA巻き戻しナイフ"としてヘリカーゼ反応に用いている新事実などが明らかとなった。

Research Products

• [Journal Article] Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN (2010)
  • Author(s): Kitano, K., Kim, SY., Hakoshima, T.
  • Journal Title: Structur 18(2) Pages: 177-187
  • Peer Reviewed
• [Journal Article] The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module. (2010)
  • Author(s): Terawaki, S., Kitano, K., Mori, T., Zhai, Y., Higuchi, Y., Itoh, N., Watanabe, T., Kaibuchi, K., Hakoshima, T.
  • Journal Title: EMBO J. 29(1) Pages: 236-250
• [Journal Article] Structural basis for CD44 recognition by ERM proteins. (2008)
  • Author(s): Mori, T., Kitano, K., Terawaki, S., Maesaki, R., Fukami, Y., Hakoshima, T.
  • Journal Title: J. Biol. Chem. 283(43) Pages: 29602-29612
• [Journal Article] Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its binding to ERM proteins. (2008)
  • Author(s): Takai, Y., Kitano, K., Terawaki, S., Maesaki, R., Hakoshima, T.
  • Journal Title: J. Mol. Biol. 381(3) Pages: 634-644
• [Journal Article] Crystallographic characterization of the membrane- targeting domains of the Rac-specific guanine nucleotide-exchange factors Tiam1 and Tiam2. (2008)
  • Author(s): Terawaki, S., Kitano, K., Hakoshima, T.
  • Journal Title: Acta Crystallogr. F. 64(11) Pages: 1039-1042
• [Journal Article] Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of membrane-type 1 matrix metalloproteinase (MT1-MMP). (2008)
  • Author(s): Terawaki, S., Kitano, K., Aoyama, M., Hakoshima, T.
  • Journal Title: Acta Crystallogr. F. 64(10) Pages: 911-913
• [Journal Article] Crystallization and preliminary crystallographic analysis of the catalytic domain of human flap endonuclease 1 in complex with a nicked DNA product. (2008)
  • Author(s): Sakurai, S., Kitano, K., Morioka, H., Hakoshima, T.
  • Journal Title: Acta Crystallogr. F. 64(1) Pages: 39-43
• [Journal Article] Crystallization and preliminary crystallographic analysis of the catalytic domain of human flap endonuclease 1 in complex with a nicked DNA product. (2008)
  • Author(s): Sakurai, S.
  • Journal Title: Acta Crystallogr., F 64(1) Pages: 39-43
  • Peer Reviewed
• [Journal Article] Structural basis for CD44 recognition by ERM proteins. (2008)
  • Author(s): Mori, T.
  • Journal Title: J. Biol. Chem. 283(43) Pages: 29602-29612
  • Peer Reviewed
• [Journal Article] Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its binding to ERM proteins (2008)
  • Author(s): Takai, Y.
  • Journal Title: J. Mol. Biol. 381(3) Pages: 634-44
  • Peer Reviewed
• [Journal Article] Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of membrane-type 1 matrix metalloproteinase (MT1-MMP). (2008)
  • Author(s): Terawaki, S.
  • Journal Title: Acta Crystallogr. F 64(10) Pages: 911-913
  • Peer Reviewed
• [Journal Article] Crystallographic characterization of the membrane- targeting domains of the Rac-specific guanine nucleotide-exchange factors Tiam1 and Tiam2. (2008)
  • Author(s): Terawaki, S.
  • Journal Title: Acta Crystallogr. F. 64(11) Pages: 1039-1042
  • Peer Reviewed
• [Journal Article] tructural basis for type II membrane protein binding by ERM proteins revealed by the radixin-neutral endopeptidase 24. 11 (NEP) complex. (2007)
  • Author(s): Terawaki, S., Kitano, K., Hakoshima, T.
  • Journal Title: J. Biol. Chem. 282(27) Pages: 19854-19862
• [Journal Article] Structural basis of PSGL-1 binding to ERM proteins. (2007)
  • Author(s): Takai, Y., Kitano, K., Terawaki, S., Maesaki, R., Hakoshima, T.
  • Journal Title: Genes Cells 12(12) Pages: 1329-1338
• [Journal Article] Spatial orientation of mitochondrial processing peptidase and a preprotein revealed by fluorescence resonance energy transfer. (2007)
  • Author(s): Nishino, TG., Kitano, K., Kojima, K., Ogishima, T., Ito, A., Kitada S.
  • Journal Title: J. Biochem. 141(6) Pages: 889-895
  • NAID: 10020098777
• [Journal Article] Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of adhesion molecule CD44. (2007)
  • Author(s): Mori T., Kitano, K., Terawaki S., Maesaki R., Hakoshima T.
  • Journal Title: Acta Crystallogr. F. 63(10) Pages: 844-847
• [Journal Article] Structural basis for type II membrane protein binding by ERM proteins revealed by the radixin-neutral endopeptidase 24.11 (NEP) complex. (2007)
  • Author(s): Terawaki, S
  • Journal Title: J. Biol. Chem. 282(27) Pages: 19854-19862
  • Peer Reviewed
• [Journal Article] Spatial orientation of mitochondrial processing peptidase and a preprotein revealed by fluorescence resonance energy transfer. (2007)
  • Author(s): Nishino, TG
  • Journal Title: J. Biochem. 141(6) Pages: 889-895
  • Peer Reviewed
• [Journal Article] Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of adhesion molecule CD44. (2007)
  • Author(s): Mori T.
  • Journal Title: Acta Crystallogr., F 63(10) Pages: 844-847
  • Peer Reviewed
• [Journal Article] Structural basis of PSGL-1 binding to ERM proteins. (2007)
  • Author(s): Takai, Y.
  • Journal Title: Genes Cells. 12(12) Pages: 1329-38
  • Peer Reviewed
• [Presentation] +TIPs, EB1-CLASP複合体結晶構造解析 (2009)
  • Author(s): 森智行, 北野健, 箱嶋敏雄
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module (2009)
  • Author(s): 寺脇慎一, 北野健, 森智行, 樋口芳樹, 伊藤教道, 渡辺崇, 貝淵弘三, 箱嶋敏雄
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] Structural basis of a novel targeting site for the specific inhibition of heterotrimeric G proteins (2009)
  • Author(s): 西村明幸, 北野健, 高崎淳, 谷口昌要, 水野憲一, 多胡憲治, 箱嶋敏雄, 伊東広
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] Tiam1/2のPHCCExドメインによる新規な細胞膜認識機構の構造生物学研究 (2009)
  • Author(s): 寺脇慎一, 北野健, 森智行, Zhai Yan, 樋口芳樹, 伊藤教道, 渡辺崇, 貝淵弘三, 箱嶋敏雄
  • Organizer: 特定領域研究「生体超分子構造」第6回公開シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2009-12-02
• [Presentation] +TIPs, EB1-CLASP複合体結晶構造解析 (2009)
  • Author(s): 森智行, 北野健, 箱嶋敏雄
  • Organizer: 特定領域研究「生体超分子構造」第6回公開シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2009-12-02
• [Presentation] +TIPs、EB1-CLASP複合体結晶構造解析 (2009)
  • Author(s): 森智行, 北野健, 箱嶋敏雄
  • Organizer: 特定領域研究「生体超分子の構造形成と機能制御の原子機構」第5回ワークショップ
  • Place of Presentation: 葉山町
  • Year and Date: 2009-07-27
• [Presentation] グアニンヌクレオチド交換因子Tiam2のPHドメインを含む新規細胞膜結合ドメインのX線結晶構造解析 (2008)
  • Author(s): 寺脇慎一, 北野健, 箱嶋敏雄
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] ヒトFEN1によるDNA認識の構造学的基盤 (2008)
  • Author(s): 櫻井滋, 北野健, 内田真希代, 森岡弘志, 箱嶋敏雄
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] グアニンヌクレオチド交換因子Tiam2のPHドメインを含む新規細胞膜結合ドメインのX線結晶構造解析 (2008)
  • Author(s): 寺脇慎一
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会)
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] ヒトFEN1によるDNA認識の構造学的基盤 (2008)
  • Author(s): 櫻井 滋
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会)
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] Structural study of the HRDC domain of human Werner syndrome protein, WRN. (2008)
  • Author(s): Kitano, K.
  • Organizer: 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens, Greece
  • Year and Date: 2008-07-03
• [Presentation] ヒトFEN1の活性促進と基質認識の構造学的基盤 (2008)
  • Author(s): 櫻井滋, 北野健, 内田真希代, 森岡弘志, 箱嶋敏雄
  • Organizer: 日本生化学会九州支部例会シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-18
• [Presentation] ヒトFEN1の活性促進と気質認識の構造学的基盤 (2008)
  • Author(s): 櫻井 滋
  • Organizer: 日本生化学会九州支部例会シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-18
• [Presentation] Structural basis for CD44 recognition by ERM proteins. (2008)
  • Author(s): Mori, T., Kitano, K., Terawaki, S., Maesaki, R., Fukami, Y., Hakoshima, T.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: Osaka, Japan
• [Presentation] Structural basis of type-II membrane protein binding by ERM proteins. (2008)
  • Author(s): Terawaki, S., Kitano, K., Hakoshima, T.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: Osaka, Japan
• [Presentation] Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. (2008)
  • Author(s): Kitano, K., Hakoshima, T.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: Osaka, Japan
• [Presentation] Crystallization and structure of human flap endonuclease 1, FEN1, in complex with a DNA product. (2008)
  • Author(s): Sakurai, S., Uchida, M., Kitano, K., Yamaguchi, H., Morioka, H., Hakoshima, T.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: Osaka, Japan
• [Presentation] Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. (2008)
  • Author(s): Kitano, K.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: 大阪国際会議場
• [Presentation] Structural basis of type-II membrane protein binding by ERM proteins. (2008)
  • Author(s): Terawaki, S.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: 大阪国際会議場
• [Presentation] Structural basis for CD44 recognition by ERM proteins. (2008)
  • Author(s): Mori, T.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: 大阪国際会議場
• [Presentation] Crystallization and structure of human flap endonuclease 1, FEN1, in complex with a DNA product. (2008)
  • Author(s): Sakurai, S.
  • Organizer: The XXI Congress and Assembly of the International Union of Crystallography (IUCr2008)
  • Place of Presentation: 大阪国際会議場
• [Presentation] ヒアルロン酸受容体である接着分子CD44とERMタンパク質との相互作用 (2007)
  • Author(s): 森智行, 北野健, 箱嶋敏雄
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-12
• [Presentation] Crystal Structure of the HRDC Domain of Human Werner Syndrome Protein, WRN. (2007)
  • Author(s): Kitano, K.
  • Organizer: The Asian Crystallographic Association (AsCA)
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2007-11-06
• [Presentation] Crystallographic characterization of the radixin FERM domain bound to cytoplasmic tail of adhesion molecule CD44. (2007)
  • Author(s): Mori, T.
  • Organizer: The Asian Crystallographic Association (AsCA)
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2007-11-06
• [Presentation] Structural study of the HRDC domain of human Werner syndrome protein, WRN (2007)
  • Author(s): Kitano, K.
  • Organizer: 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens, Greece
  • Year and Date: 2007-07-03
• [Presentation] Crystal structure of the HRDC domain bof human WRN. (2007)
  • Author(s): Kitano, K.
  • Organizer: FASEB Summer Research Conference
  • Place of Presentation: California, U.S.A.
  • Year and Date: 2007-06-24
• [Presentation] タンパク質のかたちから探る早老症 (2007)
  • Author(s): 北野健
  • Organizer: アステラス製薬研究会
  • Place of Presentation: 金沢市
  • Year and Date: 2007-06-02
• [Presentation] Crystal Structure of the HRDC Domain of Human Werner Syndrome Protein, WRN. (2007)
  • Author(s): Kitano, K., Yoshihara, N., Hakoshima, T.
  • Organizer: The 8th Conference of the Asian Crystallographic Association (AsCA2007)
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Crystallographic characterization of the radixin FERM domain bound to cytoplasmic tail of adhesion molecule CD44 (2007)
  • Author(s): Mori, T., Kitano, K., Terawaki, S., Maesaki, R., Hakoshima, T.
  • Organizer: The 8th Conference of the Asian Crystallographic Association (AsCA2007)
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Crystal structure of the HRDC domain of human WRN (2007)
  • Author(s): Kitano, K., Hakoshima, T.
  • Organizer: FASEB Summer Research Conferences "Helicases & NTP-Driven Nucleic Acid Motors: Structure, Function, Mechanisms & Roles in Human Disease"
  • Place of Presentation: Indian Wells, CA, U.S.A.