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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王勝仕(Sheng-Shih Wang) | |
dc.contributor.author | Chia-Hung Wu | en |
dc.contributor.author | 吳佳鴻 | zh_TW |
dc.date.accessioned | 2021-06-13T15:34:29Z | - |
dc.date.available | 2013-07-17 | |
dc.date.copyright | 2008-07-17 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-11 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37602 | - |
dc.description.abstract | 目前研究發現,人體中有超過二十種以上的蛋白質會因為摺疊錯誤而產生類澱粉纖維沉積,更嚴重者,甚至會造成致命性的疾病產生,而這些疾病被統稱為類澱粉症。在類澱粉症發病的過程中,蛋白質會自我聚集成富含beta-sheet結構的類澱粉纖維。雖然目前已有許多針對類澱粉纖維生成的研究結果發表,但是對於蛋白質分子結構變化的詳細機制卻仍有待釐清。
本研究利用不同的半胱胺酸及胱胺酸氧化還原組成比例,來探討氧化還原緩衝液組成對於母雞蛋白溶菌酶形成類澱粉纖維之影響。實驗中,藉由數種光學測量方法及穿透式電子顯微鏡的輔助,吾人可發現氧化還原緩衝液中的半胱胺酸可有效抑制母雞蛋白類澱粉纖維之生成。在添加有1 mM半胱胺酸的組別中,母雞蛋白類澱粉纖維的形成可受到約30 %的抑制,而添加2 mM半胱胺酸之組別,則可達到約70 %之抑制效果,因此發現半胱胺酸的抑制效果與其濃度有關,當加入之半胱胺酸濃度越高,則抑制類澱粉纖維生成之效果越佳。相對於半胱胺酸與濃度成正比的抑制效果,其氧化態之胱胺酸則僅能使類澱粉纖維生長過程中之延遲期延長,並減緩類澱粉纖維生長之速率,但對於最終生成類澱粉纖維的總量則無明顯影響。 此外,從本實驗的結果也發現,半胱胺酸的存在將使母雞蛋白溶菌酶內的雙硫鍵破壞程度增加,添加1 mM的半胱胺酸可使蛋白質內約53 %的雙硫鍵斷裂,而添加2 mM的半胱胺酸則可使蛋白質內雙硫鍵的斷裂程度提升至約79 %,這樣的趨勢與半胱胺酸抑制類澱粉纖維生成之效果類似,因此半胱胺酸抑制類澱粉纖維之形成應該與蛋白質內雙硫鍵之斷裂有關。 藉由本實驗的結果證實,當加入半胱胺酸時,蛋白質內的雙硫鍵會被破壞並達到抑制類澱粉纖維生成之效果。且由於添加2 mM半胱胺酸時,蛋白質內雙硫鍵的斷裂程度達到79 %,但其抑制類澱粉纖維生成之效果卻僅為70 %,因此在文獻的輔助下,吾人推測和母雞蛋白溶菌酶形成類澱粉纖維相關之Cys64-Cys80應該是最後一對被打斷的雙硫鍵,當此對雙硫鍵被破壞,母雞蛋白溶菌酶將不再生成類澱粉纖維。藉由本研究的結果,或許可以幫助吾人釐清在類澱粉纖維生成的過程中,具雙硫鍵的蛋白質分子結構變化及詳細機制,甚至在疾病的預防及治療上有所貢獻。 | zh_TW |
dc.description.abstract | As of now, more than twenty different human proteins can fold abnormally resulting in the formation of amyloid fibril deposits and several lethal degenerative diseases, which are called amyloidoses or amyloid diseases. During the progression of the diseases, these proteins can self-assemble into stable fibrils with extensive beta-sheet conformation. Despite extensive investigations on amyloid fibril formation, the detailed molecular mechanism remained rather elusive.
The current study is aimed at exploring the effect of varying ratio of cysteine and cystine on the fibrillogenesis of hen egg-white lysozyme. Via numerous spectroscopic techniques and transmission electron microscopy, our data revealed that the inhibition of lysozyme amyloid formation by cysteine in the redox buffer followed a concentration-dependent fashion. For instance, approximately 30 % or 70% inhibition of fibrillogenesis was observed in the presence of 1 mM or 2 mM cysteine, respectively. In contrast, the oxidized form of cysteine, cystine, nevertheless, did not influence the final level of fibrillogenesis although it lengthened the lag period and decreased the growth rate of fibril formation. Moreover, we observed in our study that the presence of cysteine led to a higher degree of disulfide bond disruption. About 53 % and 79% of disulfide bond disruptions were detected when 1 mM and 2 mM cysteine were added, respectively. It could be concluded from our results that there existed a connection between the inhibition level of fibrillogenesis and the percentage of native disulfide bond disruption for lysozyme. Our results demonstrated that the disulfide bonds could be disrupted by the addition of cysteine and thus leading to significant inhibitory effects against fibril formation. According to the results from this study and the literature, we suggested that the disulfide bridge Cys64-Cys80 which is strongly associated with lysozyme fibrillogenesis would be the last broken disulfide bond. Therefore, the fibril formation would be suppressed when this disulfide bond was broken. The outcome from this work may aid in comprehending the molecular mechanism(s) of fibrillogenesis for disulfide bond-containing amyloid proteins and development of effective therapeutics for amyloidogenic diseases. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:34:29Z (GMT). No. of bitstreams: 1 ntu-97-R95524031-1.pdf: 2501530 bytes, checksum: 5ddde5c1c92be7487263e6c76c2feea5 (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 摘要 I
Abstract III 目錄 V 圖目錄 IX 表目錄 XIII 第一章 緒論 1 第二章 文獻回顧 3 2-1 蛋白質介紹 3 2-1-1 蛋白質的結構 5 2-1-2 穩定蛋白質構造之作用力 8 2-1-3 蛋白質的構形 9 2-1-4 蛋白質的摺疊 10 2-2 聚集體 13 2-2-1 聚集體的形成 14 2-2-2 類澱粉症 17 2-3 雙硫鍵 19 2-3-1 半胱胺酸 19 2-3-2 雙硫鍵的形成與斷裂 21 2-3-3 蛋白質內雙硫鍵的生成 23 2-3-4 以DTDP測量硫醇基濃度 25 2-4 氧化還原對 27 2-4-1 氧化還原對在蛋白質復性程序上之運用 28 2-4-2 氧化還原對在類澱粉纖維生成之影響 31 2-5 溶菌酶 34 2-5-1 母雞蛋白溶菌酶簡介 34 2-5-2 母雞蛋白溶菌酶內的雙硫鍵 36 2-5-3 母雞蛋白溶菌酶形成類澱粉纖維之位置 38 2-5-4 人類溶菌酶 40 2-6 蛋白質形成類澱粉纖維之偵測方法簡介 41 2-6-1 ANS 螢光光譜方法 41 2-6-2 Congo red鍵結方法 41 2-6-3 Thioflavin T (ThT) 螢光光譜方法 42 2-6-4 圓二色光譜方法 44 2-6-5 蛋白質電泳方法 46 2-6-6 穿透式電子顯微鏡 47 第三章 研究動機 48 第四章 實驗儀器、藥品與步驟 49 4-1 實驗裝置 49 4-2 實驗藥品 50 4-3 實驗方法 52 4-3-1 ThT螢光光譜分析 52 4-3-2 ANS螢光光譜分析 52 4-3-3 Congo red鍵結分析 53 4-3-4 遠紫外光圓二色光譜分析 53 4-3-5 SDS-蛋白質電泳 53 4-3-5-1 製作SDS PAGE膠片 53 4-3-5-2 蛋白質電泳分析 55 4-3-6 穿透式電子顯微鏡 55 4-3-7 硫醇基濃度測定 55 4-3-8 HPLC分離蛋白質片段 56 4-4 實驗步驟 57 4-4-1 半胱胺酸濃度對母雞蛋白類澱粉纖維形成之影響 57 4-4-2 氧化還原緩衝液組成對母雞蛋白類澱粉纖維形成之影響 57 4-4-3 測量蛋白質內裸露的硫醇基濃度 57 4-4-4 測量溶液中的半胱胺酸濃度 58 第五章 結果與討論 59 5-1 半胱胺酸濃度對母雞蛋白類澱粉纖維形成之影響 59 5-1-1 ThT螢光光譜分析 59 5-1-2 ANS螢光光譜分析 62 5-1-3 Congo red鍵結測試 64 5-1-4 遠紫外光圓二色光譜分析 67 5-1-5 SDS蛋白質電泳分析 71 5-1-6 半胱胺酸濃度對母雞蛋白類澱粉纖維生成之影響討論 75 5-2 氧化還原緩衝液組成對母雞蛋白類澱粉纖維形成之影響 76 5-2-1 ThT螢光光譜分析 77 5-2-2 ANS螢光光譜分析 79 5-2-3 Congo red鍵結測試 81 5-2-4 遠紫外光圓二色光譜分析 86 5-2-5 SDS蛋白質電泳分析 91 5-2-6 穿透式電子顯微鏡分析 93 5-2-7 半胱胺酸及胱胺酸對母雞蛋白類澱粉纖維生成之影響討論 95 5-3 半胱胺酸與母雞蛋白溶菌酶作用之關係 97 5-3-1 以DTDP直接測量母雞蛋白溶菌酶內雙硫鍵的斷裂 97 5-3-2 半胱胺酸與母雞蛋白溶菌酶內雙硫鍵之間可能的作用關係 99 5-3-3 利用DTDP測量溶液中以各種形式存在之半胱胺酸濃度 102 5-3-4 半胱胺酸造成母雞蛋白溶菌酶內雙硫鍵斷裂之影響 106 5-3-5 空氣或溶液中存在的氧氣對抑制效果之影響 109 5-3-6 半胱胺酸與母雞蛋白溶菌酶作用之關係討論 111 5-4 母雞蛋白溶菌酶形成碎裂片段之討論 112 5-4-1 酸裂解現象對母雞蛋白溶菌酶形成碎裂片段之影響 114 5-4-2 添加半胱胺酸對母雞蛋白溶菌酶形成碎裂片段之影響 116 5-4-3 母雞蛋白溶菌酶碎裂片段對類澱粉纖維生成之影響 118 5-5 酸性環境對母雞蛋白類澱粉纖維生成之影響 119 5-5-1 酸性環境所造成之酸裂解現象 119 5-5-2 酸性環境所造成之親電子性雙硫鍵斷鍵反應 119 5-5-3 酸性環境對母雞蛋白類澱粉纖維生成之影響討論 120 第六章 結論與建議 121 6-1 實驗結論 121 6-2 建議與未來展望 125 參考文獻 126 附錄A 母雞蛋白類澱粉纖維成長動力學 136 附錄B 以DTDP測定硫醇基濃度之校正曲線 138 附錄C 母雞蛋白溶菌酶內雙硫鍵完全還原之硫醇基理論濃度計算 139 附錄D 不同時間添加半胱胺酸對母雞蛋白類澱粉纖維生成之影響 140 | |
dc.language.iso | zh-TW | |
dc.title | 氧化還原緩衝液組成對於母雞蛋白類澱粉纖維形成之影響 | zh_TW |
dc.title | Effect of Redox Buffer Composition on the Amyloid Fibrillogenesis of Hen Egg-White Lysozyme | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 劉懷勝,胡朝榮,侯劭毅,王昱麒 | |
dc.subject.keyword | 溶菌酶,類澱粉纖維,氧化還原對,半胱胺酸,胱胺酸,雙硫鍵, | zh_TW |
dc.subject.keyword | lysozyme,amyloid fibril,redox pair,cysteine,cystine,disulfide bond, | en |
dc.relation.page | 141 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-11 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 化學工程學研究所 | zh_TW |
顯示於系所單位: | 化學工程學系 |
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