1998 Fiscal Year Final Research Report Summary
Role of three dimensional structure of proteins in signal transduction
| Project/Area Number |
06276105
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
INAGAKI Fuyuhiko Tokyo Metropolitan Institute of Medical Science, Researcher, 生理活性物質研究部門, 研究員 (70011757)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Takeshi Nagoya Univ., School of Agriculture, Professor, 農学部, 教授 (10174038)
YAMAMOTO Tadashi Tokyo Univ., Institute of Medical Science, Professor, 医科学研究所, 教授 (40134621)
TAKENAWA Tadaomi Tokyo Univ., Institute of Medical Science, Professor, 医科学研究所, 教授 (40101315)
OONO Shigeo Yokohama City Univ., School of Medicine, Professor, 医学部, 教授 (10142027)
KOHDA Daisuke Biomolecular Engineering Research Institute, 研究員 (80186618)
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| Project Period (FY) |
1994 – 1997
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| Keywords | three dimensional structure of protein / NMR / X-ray crystallography / Grb2 / SH2 / SH3 / destrin / midkine |
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| Research Abstract |
The aim of the present research was to elucidate the roles of proteins in signal transduction process on the structural basis. We also developed the protein expression and purification systems for preparation of amount of proteins required for structural studies. In the course of the present research project, a number of protein structures were determined by either NMR spectroscopy or X-ray crystallography. Grb2 n-SH3 and SH2 domains complexed with proline rich peptide from Sos and phosphotyrosine containing peptide from Shc, respectively were determined and the general mechanism for recognition of target sequences were elucidated. Three dimensional structure of destrin was determined by NMR. Although the sequence homology between destrin family and gelsolin family proteins was not present, the three dimensional structure of both proteins were very similar, suggesting the same mechanism for actin severing. Thus, the general mechanism for severing of the actin fiber was proposed. The three dimensional structure of midkine was also determined by NMR and elucidated the mechanism of dimer formation on heparin oligosaccharides. The dimer formation of midkine seems to be essential for activation of the receptor and its biological function. We also determined the CRD domain of PKC and suggested the mechanism of DAG recognition. By X-ray crystallography, a number of protein structures were determined including transmitter and receiver domains of bacterial signal transduction system. We also made protein expression and purification system for N-WASP, Tob and CAF1. N-WASP is essential for formation of philopodia in response to the growth factor receptor signal. Tob and CAF1 play pivotal role in cell cycling. The structural studies started for both proteins.
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[Publications] Kohda, D., Terasawa, H., Ichikawa, S., Ogura, K., Hatanaka, H., Mandiyan, V., Ullrich, A., Schlessinger, J. and Inagaki, F.: "Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2"Structure. 2. 1029-1040 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Terasawa, H., Kohda, D., Hatanaka. H., Tsuchiya, S., Ogura, K., Nagata, K., Ishii, S., Mandiyan, V., Ullrich, A., Schlessinger, J. and Inagaki, F.: "Structure of the N-terminal SH3 domain of GRB2 complexed with a peptide from the guanine nucleotide releasing factor Sos"Nature structural biology. 1. 891-897 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hatanaka, H., Ogura, K., Moriyama, K., Ichikawa, S., Yahara, I. and Inagaki, F.: "Tertiary Structure of Destrin and Structural Similarity between Two Actin-Regulating Protein Families"Cell. 85. 1047-1055 (1996)
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[Publications] Kohda, D., Morton, C. J., Parker, A. A., Hatanaka, H., Inagaki, F., Campbell, I. D. and Day, A. J.: "Solution Structure of the Link Module : A Hyaluronan-Binding Domain Involved in Extracellular Matrix Stability and Cell Migration"Cell. 86. 767-775 (1996)
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[Publications] Iwasaki, W., Nagata, K., Hatanaka, H., Inui, T., Kimura, T., Muramatsu, T., Yoshida, K., Tasumi, M. and Inagaki, F.: "Solution structure of midkine, a new heparin-binding growth factor"EMBO J.. 16. 6936-6946 (1997)
Description
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[Publications] Umemori, H., Inoue, T., Kume, S., Sekiyama, N., Nagao, M., Itoh, H., Nakanishi, S., Mikoshiba, K. and Yamamoto, T: "Activation of the G protein Gq/11 through turosine phosphorylation of the a subunit"Science. 276. 1878-1881 (1997)
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[Publications] Yasue, T., Nishizumi, H., Miyake, K., Aizawa, S., Yamamoto, T., Uehara, S., Kikuchi, Y. and Takatsu, K.: "IgG1 production induced by CD38 ligation and IL-5 require activation of Fyn and Lyn kinases"Proc. Natl. Acad. Sci. USA94. 10307-10312 (1997)
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[Publications] Lu, Z., Hornia, A., Jiang, Y-W., Frankel, P., Zang Q., Ohno, S. and Foster, D., A.: "Tumor-promotion by deple＼＼ting cells of protein kinase Cd."Molecular and Cellular Biol.. 17. 3418-3428 (1997)
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[Publications] Ames, J. B., Ishima, R., Tanaka, T., Gordon, J. I., Stryer, L. and Ikura, M.: "Molecular mechanics of calcium-myristoyl switches"Nature. 389. 198-202 (1997)
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「研究成果報告書概要(欧文)」より
