Structural basis for the activation of Rab GTPases

• Project/Area Number: 19770078
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: FUKAI Shuya The University of Tokyo, 放射光連携研究機構, 准教授 (10361792)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: X線結晶構造解析 / 低分子量GTPase / 分子間相互作用 / 膜タンパク質 / 小胞輸送 / 膜融合 / グアニンヌクレオチド交換因子

Research Abstract

真核細胞は、脂質膜で囲まれた様々な細胞内小器官から構成されており、その間を多種多様な生体高分子が、小胞と呼ばれる小さな袋を介して行き来している。この小胞による輸送の制御には、分子スイッチとして機能するRabタンパク質が必要である。本研究では、Rabタンパク質のスイッチをONにする(活性化する)メカニズムを原子レベルで解明することを目的として、Rabタンパク質とその活性化タンパク質との複合体の立体構造を決定した。

Research Products

• [Journal Article] Conformational transition of Sec machinery inferred from bacterial SecYE structures (2008)
  • Author(s): Tsukazaki, T., Mori, H., Fukai, S., Ishitani, R., Mori, T., Dohmae, N., Perederina, A., Sugita, Y., Vassylyev, D. G., Ito, K., Nureki, O
  • Journal Title: Nature 455 Pages: 988-991
• [Journal Article] Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains (2008)
  • Author(s): Sato, Y., Yoshikawa, A., Yamagata, A., Mimura, H., Yamashita, M., Ookata, K., Nureki, O., Iwai, K., Komada, M., Fukai, S
  • Journal Title: Nature 455 Pages: 358-362
• [Journal Article] Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanous-related formins, mDia1 and Daam1, in platelets (2008)
  • Author(s): Higashi, T. Ikeda, T., Shirakawa, R., Kondo, H., Kawato, M., Horiguchi, M. Okuda, T., Okawa, K., Fukai, S., Nureki, O., Kita, T., Horiuchi, H
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 8746-8756
• [Journal Article] Regulation of platelet dense granule secretion by the Ral GTPase-Exocyst pathway (2008)
  • Author(s): Kawato, M., Shirakawa, R., Kondo, H., Higashi, T., Ikeda, T., Okawa, K., Fukai, S., Kita, T., Horiuchi, H
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 166-174
• [Journal Article] Conformational transition of Sec machinery inferred from bacterial SecYE structures (2008)
  • Author(s): Tsukazaki, T., Mori, H., Fukai, S., Ishitani, R., Mori, T., Dohmae, N., Perederina, A., Sugita, Y., Vassylyev, D. G., Ito, K., Nureki, O.
  • Journal Title: Nature 455 Pages: 988-991
  • Peer Reviewed
• [Journal Article] Structural basis for specific cleavage of Lys 63- linked polyubiquitin chains (2008)
  • Author(s): Sato, Y., Yoshikawa, A., Yamagata, A., Mimura, H., Yamashita, M., Ookata, K., Nureki, O., Iwai, K., Komada, M., Fukai, S.
  • Journal Title: Nature 455 Pages: 358-362
  • Peer Reviewed
• [Journal Article] Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanous-related formins, mDial and Daaml, in platelets (2008)
  • Author(s): Higashi, T. Ikeda, T., Shirakawa, R., Kondo, H., Kawato, M., Horiguchi, M. Okuda, T., Okawa, K., Fukai, S., Nureki, O., Kita, T., Horiuchi, H.
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 8746-8755
  • Peer Reviewed
• [Journal Article] Regulation of platelet dense granule secretion by the Ral GTPase-Exocyst pathway (2008)
  • Author(s): Kawato, M., Shirakawa, R., Kondo, H., Higashi, T., Ikeda, T., Okawa, K., Fukai, S., Kita, T., Horiuchi, H.
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 166-174
  • Peer Reviewed
• [Journal Article] Crystal structure of human DAAM1 formin homology 2 domain (2007)
  • Author(s): Yamashita, M., Higashi, T., Suetsugu, S., Sato, Y., Ikeda, T., Shirakawa, R., Kita, T., Takenawa, T., Horiuchi, H., Fukai, S., Nureki, O
  • Journal Title: Genes to Cells 12巻 Pages: 1255-1265
• [Journal Article] Crystal structure of the Sec2p-Sec4p complex in the intermediate state of the nucleotide exchange reaction (2007)
  • Author(s): Sato, Y., Fukai, S., Ishitani, R.,Nureki, O
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A 104巻 Pages: 8305-8310
• [Journal Article] Crystallization and crystallographic analysis of yeast Sec2p, a guanine nucleotide-exchange factor for the yeast Rab GTPase Sec4p (2007)
  • Author(s): Sato, Y., Fukai, S., Nureki, O
  • Journal Title: Acta Crystallographica F63巻 Pages: 616-619
• [Journal Article] Crystal structure of human DAAMI formin homology 2 domain (2007)
  • Author(s): Yamashita, M., Higashi, T., Suetsugu, S., Sato, Y., Ikeda, T., Shirakawa, R., Kita, T., Takenawa, T., Horiuchi, H., Fukai, S., Nureki, O.
  • Journal Title: Genes to Cells 12 Pages: 1255-1265
  • Peer Reviewed
• [Journal Article] Crystal structure of the Sec2p-Sec4p complex in the intermediate state of the nucleotide exchange reaction (2007)
  • Author(s): Sato, Y., Fukai, S., Ishitani, R., Nureki, O.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A 104 Pages: 8305-8310
  • Peer Reviewed
• [Journal Article] Crystallization and crystallographic analysis of yeast Sec2p, a guanine nucleotide-exchange factor for the yeast Rab GTPase Sec4p (2007)
  • Author(s): Sato, Y., Fukai, S., Nureki, O.
  • Journal Title: Acta Crystallographica F 63 Pages: 616-619
  • Peer Reviewed
• [Presentation] AMSHファミリーによるK63結合型ポリユビキチン鎖特異的な切断活性機構の構造的基盤 (2008)
  • Author(s): 佐藤裕介
  • Organizer: BMB2008
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-12
• [Presentation] Structural basis of selective cleavage of Lys63-linked polyubiquitin chains by JAMM ubiquitin isopeptidase (2008)
  • Author(s): 深井 周也
  • Organizer: FASEB Summer Research Conferences -Ubiquitin and Cellular Regulation-
  • Place of Presentation: Saxton's River, Vermont, USA
  • Year and Date: 2008-06-16
• [Presentation] Structural basis of selective cleavage of Lys63-linked polyubiquitin chains by JAMM ubiquitin isopeptidase (2008)
  • Author(s): 深井周也
  • Organizer: FASEB Summer Research Conferences Ubiquitin and Cellular Regulation
  • Place of Presentation: Saxton's River, Vermont, USA
  • Year and Date: 2008-06-16
• [Presentation] 開口放出を制御するRabGTPase Sec4p活性化の構造的基盤 (2007)
  • Author(s): 深井周也
  • Organizer: BMB2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Presentation] RalGAPの同定 (2007)
  • Author(s): 白川龍太郎
  • Organizer: BMB2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Presentation] Rhoによって制御される細胞質中のForminタンパク質によるアクチン重合 (2007)
  • Author(s): 東智仁
  • Organizer: BMB2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-12
• [Book] 実験医学2月号 (2009)
  • Author(s): 深井周也、佐藤裕介、吉川梓
  • Publisher: 羊土社