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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 許 輔(Fuu Sheu) | |
dc.contributor.author | Yu-Shan Lin | en |
dc.contributor.author | 林瑜珊 | zh_TW |
dc.date.accessioned | 2021-05-15T17:53:53Z | - |
dc.date.available | 2017-08-25 | |
dc.date.available | 2021-05-15T17:53:53Z | - |
dc.date.copyright | 2014-08-25 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-07-30 | |
dc.identifier.citation | 水野卓、川合正允。(1997)。菇類的化學、生化學。臺北市:國立編譯館。
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Dimerization of the N-terminal amphipathic alpha-helix domain of the fungal immunomodulatory protein from Ganoderma tsugae (Fip-gts) defined by a yeast two-hybrid system and site-directed mutagenesis. J Biol Chem, 272(32):20044-20048. Liu, Y. F., Chang, S. H., Sun, H. L., Chang, Y. C., Hsin, I. L., Lue, K. H., and Ko, J. L. (2012). IFN-gamma induction on carbohydrate binding module of fungal immunomodulatory protein in human peripheral mononuclear cells. J Agric Food Chem, 60(19):4914-4922. Ohkuma, T., Otagiri, K., Ikekawa, T., and Tanaka, S. (1982). Augmentation of antitumor activity by combined cryo-destruction of sarcoma 180 and protein-bound polysaccharide, EA6, isolated from Flammulina velutipes (Curt. ex Fr.) Sing. in ICR mice. J Pharmacobiodyn, 5(6):439-444. Otagiri, K., Ohkuma, T., Ikekawa, T., and Tanaka, S. (1983). Intensification of antitumor-immunity by protein-bound polysaccharide, EA6, derived from Flammulina velutipes (Curt. ex Fr.) 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Purification and cDNA cloning of a protein derived from Flammulina velutipes that increases the permeability of the intestinal Caco-2 cell monolayer. European Journal of Biochemistry, 262(3):850-857. Yoshioka, Y. , Sano, T. , and Ikekawa, T. (1973). Studies on antitumor polysaccharides of Flammulina velutipes (Curt. ex Fr.) Sing. I. Chem Pharm Bull (Tokyo). 21(8):1772-1176. Zhang, H., Gong, F., Feng, Y., and Zhang, C. (1999). Flammulin Purified from the Fruit Bodies of Flammulina velutipes (Curt.:Fr.) P.Karst. 1(1):89-92. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5225 | - |
dc.description.abstract | 金針菇免疫調節蛋白 FIP-fve 萃取自金針菇子實體,文獻指出其具有免疫調節、抗癌、抗過敏及減緩發炎反應等功效。二級結構分析顯示,FIP-fve 透過兩個單元體 N 端 α-helix 以疏水性鍵結形成雙元體。本實驗室前人研究指出 FIP-fve 不需經過抗原呈獻細胞修飾,而是透過與 MHC 及 TCR 分子鍵結活化 T 細胞,因此推測FIP-fve 作用方式類似超抗原。本研究目的有二,一為證實雙元體結構對於 FIP-fve 的免疫調節活性是必要的,二為找出 FIP-fve 與 MHC 和 TCR 具交互作用之證據。為探討雙元體結構對 FIP-fve 免疫調節活性之影響,將 1-13 胺基酸缺失或全長 FIP-fve cDNA構築於 pET-32a(+) 載體,並透過大腸桿菌系統表現得分子量皆約 26 kDa 之 His-FIP-fve 1-114 和 His-FIP-fve 14-114 蛋白。以 enterokinase 切除 His-tag 後,經質譜比對確認成功取得 rFIP-fve 1-114 以及 rFIP-fve 14-114。免疫調節活性試驗方面,片段缺失 rFIP-fve 14-114 刺激小鼠脾臟細胞分泌 IFN-γ 能力較 rFIP-fve 1-114 弱,且無法刺激小鼠脾臟細胞 IFN-γ 及 IL-2 基因表現。綜合以上結果,推測失去雙元體結構造成 FIP-fve 免疫調節活性降低。在 FIP-fve 類超抗原性質探討上,透過共同免疫沉澱法可知 FIP-fve 與表面分子 MHC class II 具交互作用,另外發現 FIP-fve 可被 MHC class I 及其 Isotype IgG2a 抗體捕捉。然而,本研究尚未透過共同免疫沉澱法看見 FIP-fve 與 TCR 連結之證據,因此僅能證實 FIP-fve 能連結 APCs 表面分子 MHC class II。 | zh_TW |
dc.description.abstract | FIP-fve, an immunomodulatory protein isolated from Flammulina velutipes, has been demonstrated to have activities of immunomodulatory, anti-cancer, anti-allergic and suppression of inflammation. Based on a secondary structure analysis, we known that two FIP-fve monomers form homodimer through the hydrophobic interaction between N-terminal α-helics. Previous studies suggested that FIP-fve can mediate T cells activation through the linkage between T cell receptors (TCR) on T cells and MHC molecules on antigen present cells (APCs) without processing procedure of APCs. This process is similar to the mechanism of superantigen-mediated immune response. The aim of this study was to demonstrate the necessity of dimer structure for FIP-fve immunomodulatory activity and to prove the directly binding of FIP-fve with MHC and TCR. To study the relationship between the dimer structure and immunomodulatory activity of FIP-fve, we constructed the full length 1-114 FIP-fve cDNA and truncated 14-114 FIP-fve cDNA on pET-32a(+) vector and expressed the His-fusion protein His-FIP-fve 1-114 and His-FIP-fve 14-114. After digested by enterokinase to remove the His-tag residue, rFIP-fve 1-114 and rFIP-fve 14-114 were purified with FPLC system. The ability of rFIP-fve 14-114 to stimulate IFN-γ production on murine splenocytes was lower than rFIP-fve 1-114. Incubating murine splenocytes with rFIP-fve 14-114 could not elevate the gene expression of IFN-γ and IL-2. According to the above results, we suggested that the dimerization might be critical for FIP-fve immunomodulatory activity. On the other hand, FIP-fve and RAW 264.7 cell lysate were co-immunoprecipitated to determine superatigen-like characterization of FIP-fve. Results indicated that FIP-fve could interact with MHC class II molecule directly. Interestingly, we also found that FIP-fve was pulled down by both anti-MHC class I antibody and IgG2a which was isotype of anti-MHC class I antibody. However, no co-immunoprecipitated evidence showed that FIP-fve bound with TCR in this study. In conclusion, we proved that FIP-fve directly bind with MHC class II molecule. | en |
dc.description.provenance | Made available in DSpace on 2021-05-15T17:53:53Z (GMT). No. of bitstreams: 1 ntu-103-R01628205-1.pdf: 4501145 bytes, checksum: 7af86104ccac194ed62de773d47a2b16 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員會審定書 I
致謝 II 摘要 IV Abstract V 目錄 VII 圖目錄 IX 縮寫表 X 第一章 前人研究 1 第一節 金針菇簡介 1 第二節 其他金針菇成分與功效介紹 2 第三節 金針菇免疫調節蛋白 FIP-fve 簡介 5 第四節 超抗原簡介 10 第二章 研究動機與目的 12 第三章 材料與方法 13 第一節 金針菇免疫調節蛋白 FIP-fve 純化 14 第二節 變性膠體電泳分析 (SDS-PAGE) 17 第三節 蛋白質濕式轉印 19 第四節 西方轉漬法 (western blotting) 20 第五節 重組蛋白 rFIP-fve 1-114 及truncated rFIP-fve 14-114 基因選殖與構築 21 第六節 重組蛋白 rFIP-fve 1-114 及truncated rFIP-fve 14-114 表現與純化 25 第七節 膠體內水解 (In gel digestion) 27 第八節 小鼠脾臟細胞取得 28 第九節 酵素連結免疫吸附分析 (Enzyme-linked immunosorbent assay, ELISA) 30 第十節 細胞總 RNA 抽取與反轉錄 31 第十一節 即時定量聚合酶鏈鎖反應 (Real-time PCR) 32 第十二節 巨噬細胞株 RAW 264.7 細胞培養 34 第十三節 共同免疫沉澱法 (Co-immunoprecipitation) 35 第十四節 統計分析 38 第四章 研究結果 39 第一節 重組蛋白 rFIP-fve 1-114 及 truncated rFIP-fve 14-114 選殖與純化 39 第二節 重組蛋白 rFIP-fve 1-114 及 truncated rFIP-fve 14-114 於小鼠脾臟細胞之免疫活性 42 第三節 以共同免疫沉澱法探討 FIP-fve 之類超抗原特性 43 第五章 討論 46 第一節 重組蛋白 rFIP-fve 1-114 及 truncated rFIP-fve 14-114 蛋白純化探討 46 第二節 片段缺失 truncated rFIP-fve 14-114 蛋白功能探討 47 第三節 FIP- fve 與表面分子親和性之探討 48 第六章 結論與未來展望 51 參考文獻 52 | |
dc.language.iso | zh-TW | |
dc.title | FIP-fve 蛋白之 N 端序列對其免疫活性之必要性 | zh_TW |
dc.title | N-terminal of FIP-fve is essential for its immune activity | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 周志輝,潘敏雄,繆希椿 | |
dc.subject.keyword | 超抗原,His 融合蛋白,同型雙元體,免疫調節蛋白,共同免疫沉澱, | zh_TW |
dc.subject.keyword | superantigen,His-fusion protein,homodimer,immunomodulatory protein,co-immunoprecipitation, | en |
dc.relation.page | 74 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2014-07-30 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 園藝學研究所 | zh_TW |
顯示於系所單位: | 園藝暨景觀學系 |
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