2001 Fiscal Year Final Research Report Summary
Protein-protein interaction in intracellular signal transduction
| Project/Area Number |
10179104
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Hokkaido University (1999-2001)
Tokyo Metropolitan Organization for Medical Research (1998) |
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Principal Investigator |
INAGAKI Fuyuhiko Hokkaido University, professor -> 北海道大学, 大学院・薬学研究科, 教授 (70011757)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKITA Shoichiro Kyoto University, professor, 大学院・医学研究科, 教授 (50155347)
YAMAMOTO Tadashi Tokyo University, professor, 医科学研究所, 教授 (40134621)
TAKENAWA Tadaomi Tokyo University, professor, 医科学研究所, 教授 (40101315)
KOHDA Daisuke Kyushu University, professor, 生体防御医学研究所・バイオサイエンス研究, 教授 (80186618)
HAKOSHIMA Toshio Nara Institute of Science and Technology, professor, バイオサイエンス研究科, 教授 (00164773)
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| Project Period (FY) |
1998 – 2001
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| Keywords | Vav / SH3 / Grb2 / praline rich region / tertiary structure IP3 / radixin / IP3 / PTB様ドメイン |
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| Research Abstract |
Vav is a guanine nucleotide exchange factor for the Rho/Rac family that is expressed exclusively in hematopoietic cells. Growth factor receptor-bound protein 2 (Grb2) has been proposed to play important roles in the membrane localization and activation of Vav through dimerization of its C-terminal Srchomology 3 (SH3) domain (GrbS) and the N-terminal SH3 domain of Vav (VavS). The crystal strucuture of VavS complexed with GrbS has been solved. VavS is distinct from other SH3 domain proteins in that its binding site for proline-rich peptides is blocked by its own RT loop. One of the ends of the VavS β-barrel forms a concave hydrophobic surface. The GrbS components make a contiguous complementary interface with the VavS surface. The binding site of GrbS for VavS partially overlaps with the canonical binding site for proline-rich peptides, but is definitely different. Mutations at the interface caused a decrease in the binding affinity of VavS for GrbS by 4- to 40-fold. The structure reveals how GrbS discriminates VavS specifically from other signaling molecules without binding to the proline-rich motif.
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Research Products
(12 results)
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[Publications] Panting, C. P., Ito, T., Moscat, J., Diaz-Mew, M., Inagaki, F., Sumimoto, H.: "OPR, PC and AID : all in the PB1 femily"TIBS. 27. 10 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ogura, K., Nagata, K., Horiuchi, M., Ebisui, E., Hasuda, T., Yuzawa, S., Nishida, M., Hatanaka, H., Inagaki, F.: "Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain"J. Biomal. NMR. 22. 37-46 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Terasawa, H., Noda, Y., Ito, T., Hatanaka, H., Ichikawa, S., Ogura, K., Sumimoto, H., Inagaki, F.: "Structure and ligand recognition of the PBI domain : A novel protein modulebinding to the PC motif"EMBO J., 20. 15. 3947-3956 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nishida, M., Nagata, K., Hachimori, Y., Horiuchi, M., Ogura, Mandiyan, K. V., Schlessinger, J., Inagaki, F.: "Novel recognition mode between Vav and Grb2 SH3 domains"EMBO J. 20. 12. 2995-3007 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yuzawa, S., Yokochi, M., Hatanaka, H., Ogura, K., Kataoka, M., Miura, K., Mandiyan, K. V., Schlessinger, J., Inagaki, F.: "Solution structure of Grb2 reveals extensive flexisibility necessary for recognition"J. Mol. Biol.. 306. 527-537 (2001)
Description
「研究成果報告書概要(欧文)」より
