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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81142完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁博煌(Po-Huang Liang) | |
| dc.contributor.author | Hsin-Ying Ho | en |
| dc.contributor.author | 何欣穎 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:32:43Z | - |
| dc.date.available | 2021-08-20 | |
| dc.date.available | 2022-11-24T03:32:43Z | - |
| dc.date.copyright | 2021-08-20 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-10 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81142 | - |
| dc.description.abstract | X染色體連鎖凋亡抑制蛋白（XIAP）為一多功能蛋白質，屬於IAP蛋白家族，其最大的特點是具有抗細胞凋亡的功能，藉由與caspase-3 結合能夠直接抑制其活性。矛盾的是，caspase-3 能夠於特定位點(Asp242)將XIAP切割成兩個片段，從而減弱 XIAP 對細胞凋亡的抑制。而先前的研究證據顯示，XIAP 能夠與未完全活化的caspase-3 p20/p12結合，使其停留在該型態而無法透過自催化作用活化成p17/p12。本篇研究提出 XIAP 主要藉由與 caspase-3 p20/p12 相互作用來抑制 caspase-3 活性，阻止其完全活化，而非直接抑制有活性的 caspase-3。對於成熟的 caspase-3，XIAP 是被其水解的受質，該水解會導致其功能之喪失。在本篇研究中發現，與成熟的 p17/p12 相比，XIAP 對 caspase-3 p20/12 表現出更高的親和力，這表明 XIAP 與這兩種形式的 caspase-3 之間的結合模式可能是不同的。為了證明這個想法，我純化了 XIAP/caspase-3 複合物（XIAP/caspase-3 p20/p12 和 XIAP/caspase-3 /p17/p12），並嘗試利用冷凍電子顯微鏡解析其結構。利用戊二醛(glutaraldehyde)將蛋白複合體進行交叉鍵接(cross-link)反應，穩定XIAP/caspase-3 p20/p12複合體後，我們得到一低解析度(~12Å)的三維重建。後續研究將繼續專注於解析出高解析度的 XIAP/caspase-3 複合物的結構，以闡明 XIAP 與 caspase-3 之間的相互作用。 | zh_TW |
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| dc.description.tableofcontents | "口試委員會審定書 I Acknowledgements II 中文摘要 III Abstract IV Table of Contents VI List of Abbreviations IX List of Figures XI List of Tables XIII Chapter 1 Introduction 1 1.1 Background to the research 1 1.1.1 Apoptosis 1 1.1.2 Inhibitor of apoptosis protein (IAP) family 3 1.1.3 X-linked inhibitor of apoptosis protein (XIAP) 4 1.1.4 Caspase-3 6 1.2 Motivation of Research 7 1.3 Literature review 10 1.3.1 XIAP was reported to be a direct inhibitor of caspase-3, -7, and -9 10 1.3.2 XIAP cleavage by caspase-3 was observed in several studies 11 1.3.3 Caspase-3 was shown to be arrested in its intermediate state by XIAP 14 1.3.4 The IBM of caspase-9 was demonstrated to be removed by caspase-3, relieving the inhibition exerted by XIAP 15 1.3.5 Previous structural analysis on XIAP/caspase-3 interaction 16 1.4 Hypothesis 18 1.5 Specific aims of this study 20 Chapter 2 Materials and Methods 22 2.1 Plasmids 22 2.2 Expression and purification of recombinant proteins 23 2.3 Analytical ultracentrifugation (AUC) 25 2.4 Isothermal titration calorimetry (ITC) 26 2.5 Initial screening of protein crystallization conditions 27 2.6 Preparation of Cross-linked protein complex samples 27 2.7 Cryo-EM grids preparation and data collection 27 2.8 Caspase-3 p20/p12 activation assay 28 Chapter 3 Results 29 3.1 Expression and purification of recombinant proteins 29 3.1.1 Trx-XIAP and XIAP 29 3.1.2 Caspase-3 32 3.1.3 XIAP/Caspase-3 complex 33 3.2 Characterizing the stoichiometry of XIAP/caspase-3 complex 33 3.3 XIAP has a higher affinity for partially processed caspase-3 than mature caspase-3 34 3.4 Protein crystallization 35 3.5 Cryo-EM single particle reconstruction (SPR) of XIAP/caspase-3 p20/p12 complex 36 3.6 Aggregation of Caspase-3 p20/p12 occurs in salt-free environment 37 3.7 The autocatalytic competence of caspase-3 p20/p12 is modulated by salt in vitro 38 Chapter 4 Discussion 40 Figures 44 Tables 70 References 72 " | |
| dc.language.iso | en | |
| dc.subject | 冷凍電子顯微鏡 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | X染色體連鎖凋亡抑制蛋白 | zh_TW |
| dc.subject | 凋亡蛋白酶 | zh_TW |
| dc.subject | 蛋白質複合體 | zh_TW |
| dc.subject | Caspase-3 autocatalysis | en |
| dc.subject | cryo-EM | en |
| dc.subject | XIAP/Caspase-3 complex | en |
| dc.subject | apoptosis | en |
| dc.subject | XIAP | en |
| dc.title | 利用結構生物學探討XIAP與Caspase-3之間的相互抑制作用 | zh_TW |
| dc.title | Structural Analysis on the Reciprocal Inhibition Between XIAP and Caspase-3 | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 袁小琀(Hsin-Tsai Liu),林世昌(Chih-Yang Tseng) | |
| dc.subject.keyword | 細胞凋亡,X染色體連鎖凋亡抑制蛋白,凋亡蛋白酶,蛋白質複合體,冷凍電子顯微鏡, | zh_TW |
| dc.subject.keyword | XIAP,Caspase-3 autocatalysis,apoptosis,XIAP/Caspase-3 complex,cryo-EM, | en |
| dc.relation.page | 81 | |
| dc.identifier.doi | 10.6342/NTU202102192 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-12 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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