Structural biology of cytoskeletal control by dynamic protein complex formation.

2010 Fiscal Year Final Research Report

• Project/Area Number: 19207010
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: HAKOSHIMA Toshio Nara Institute of Science and Technology, 情報科学研究科, 教授 (00164773)
• Co-Investigator(Kenkyū-buntansha): MISHIMA Masaki 首都大学東京, 理工学研究科, 准教授 (70346310)
• Project Period (FY): 2007 – 2010
• Keywords: 構造生物学 / 細胞生物学 / X線結晶学 / シグナル伝達 / がん / 転移 / 浸潤 / 植物ホルモン

Research Abstract

We pursued structural studies of signaling proteins important in cell biology and enzymes that play a role in maintenance of genome stability. Using X-ray crystallography and NMR, we revealed three-dimensional structures of the PH-C1-PH domain of Rho-kinase, the radixin FERM domain-CD44 complex, the PHCCEx domain of RacGEF Tiam1,the CAP-Gly domain of CLIP-170 complexed with the acidic tail of α-tubulin, the gibberellin receptor bound to the effector protein DELLA, the trimeric G protein Gq-YM254890 complex and the WRN-DNA complex and elucidated their structure-function relationships at atomic resolution.

Research Products

• [Journal Article] The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-targeting 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
  • Peer Reviewed
• [Journal Article] Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule. (2010)
  • Author(s): Nishimura, A., Kitano, K., Takasaki, J., Taniguchi, M., Mizuno, M., Tago K., Hakoshima, T., Itoh, H.
  • Journal Title: Proc.Natl.Acad.Sci.USA 107(31) Pages: 13666-13671
  • Peer Reviewed
• [Journal Article] Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicalse WRN. (2010)
  • Author(s): Kitano, K.Kim, S.Y., Hakoshima, T.
  • Journal Title: Structure (Cell Press). 18(2) Pages: 177-187
  • Peer Reviewed
• [Journal Article] Gibberellin-induced DELLA recognition by the gibberellin receptor GID1 (Article). (2008)
  • Author(s): Murase, K., Hirano, Y., Sun, T.-p., Hakoshima, T.
  • Journal Title: Nature 456(7221) Pages: 459-463
  • 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., Kitano, K., Terawaki, S., Maesaki, R., *Hakoshima, T.
  • Journal Title: J.Mol.Biol. 381(3) Pages: 634-644
  • Peer Reviewed
• [Journal Article] A molecular mechanism of P-loop pliability of Rho-kinase investigated by molecular dynamic simulation. (2008)
  • Author(s): Gohda, K., *Hakoshima, T.
  • Journal Title: Journal of Computer-aided Molecular Design 22(11) Pages: 789-797
  • Peer Reviewed
• [Journal Article] Structural properties of the cytoplasmic tail of adhesion molecule CD44 and its binding to FERM proteins. (2008)
  • Author(s): Mori, T., itano, K., Fukami, Y., Terawaki, S., Hakoshima, T.
  • Journal Title: J.Biol.Chem. 283(43) Pages: 29602-29612
  • Peer Reviewed
• [Journal Article] Structural basis for tubulin recognition by cytoplasmic linker protein 170 and its autoinhibition. (2007)
  • Author(s): Mishima, M., Maesaki, R., Kasa, M., Watanabe, T., Fukata, M., Kaibuchi, K., Hakoshima, T.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 104(25) Pages: 10346-10351
  • Peer Reviewed
• [Journal Article] Structural basis for type II membrance 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: 19854-19861
  • Peer Reviewed
• [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 to Cells 12(12) Pages: 1329-1338
  • Peer Reviewed
• [Journal Article] Chapter III.P-loop pliability of Rho-kinase for inhibitor binding. In (2007)
  • Author(s): Gohda, K., Hakoshima, T.
  • Journal Title: Drug Design Research Perspectives (Nova Science Publishers, Inc.) (Review) Pages: 39-55
  • Peer Reviewed
• [Remarks] ホームページ等