Analysis of structure and serch for new function of novel recombinant glycoprotein hormones
| Project/Area Number |
07807097
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Koshien University College of Nutrition |
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Principal Investigator |
MIYAI Kiyoshi Koshien University College of Nutrition Professor, 栄養学部, 教授 (30028394)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | glycoprotein hormone / mutant glycoprotein hormone alpha subunit / thyrotropin (TSH) / chorionic gonadotropin / immunological activity / tertiary structure / CXGXC motif / cholera toxin / 絨毛性ゴナドトロピン |
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| Research Abstract |
Relationship between tertiary structure and function of novel bioactive peptides was analyzed to serch for their new functions.
1. Nature of novel recombinant glycoprotein hormones-Effect of mutation in the CMGCC region of the alpha subunit on immunoreactive TSH-Immunoreactive TSH was detectable in culture media of COS-1 cell co-transfected with wild type beta subunit and alpha subunit (CMGCC) or mutant alpha subunit (CRGCC) , but not in other mutants (YMGCC) (CMRCC) , (CMACC) , (CMDCC) , supporting our hypothesis that an amino acid motif of CXGXC in common alpha (CMGCC) and beta (CAGYC) subunits play an important role in biosynthesis of glycoprotein hormones.
2. Nature of novel recombinant bioactive peptides-Mutant cholera toxin with mutation in the CAEYH region of B subunit-Biological activity (morphological changes and accumlation of CAMP in CHO cells) was detectable in wild type (CAEYH) and mutant (CAGYH) , but not in mutant (CARYH) cholers toxin.
3. Serch for novel mutant glycoprotein hormones-Ectopic production of hCG-Serum hCG elevated in an acromegalic patient was analyzed by the dilution experiment and the recovery test excluding non specific interference.
4. Analysis of three dimensional structure of glycoprotein hormones-Three dimensional structure of hCG was illustrated by computer graphics indicating that amino acid residues were well arranged in wild type (alpha : CMGCC) and a mutant (alpha : CRGCC) , but not in a mutant (alpha : CMDCC) hCG.
Further studies are reuired to elucidate the significance and mechanism of the motif CXGXC to serch bioactiuve peptides with novel functions.
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Report
(4 results)
Research Products
(17 results)
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[Publications] Yamaoka, JI., Yamasaki, S., Kurazono, H., Imamura, S., Noda, M., Miyai. K., Takeda, Y. :"Loss of biological activity duo to Glu*Arg mutation at residue 11 of the B subunit of cholera toxin" Microbial Pathogenesis. 23 (5). 297-302 (1997)
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Related Report
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[Publications] Miyai, K., Kumazawa, I., Saji, F., Azuma, C., Koyama, M., Kimura, T., Narizuka, M., Murata, Y. :"Effect of site directed mutagenesis in the CMGCC region of the alpha-subunit on immunoreactive human thyrotropin." Endocr J. 45 (4) (in press). (1998)
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[Publications] Miyai, K.: Isolated TSH deficiency. In Kosho, T., Imura, H., Nakagone, Y., Okada, S., Yuasa, Y., Kurata, T., eds Clinical DNA Diagnosis. Kanahara Pub, Tokyo, 495-500 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Miyai, K.: Synthesis and abnormality of pituitary hormones. In Takaku, F., Yazaki, Y., Saruta, T., Shishiba, Y., eds Illustranted Medicine Illustrated Internal Medicine 12 Endocrinology and Metabolism. Medical View, Tokyo, 132-143 (1995)
Description
「研究成果報告書概要(欧文)」より
Related Report
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