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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張祟毅 | |
| dc.contributor.author | Ming-Yuan Su | en |
| dc.contributor.author | 蘇明媛 | zh_TW |
| dc.date.accessioned | 2021-06-07T17:58:20Z | - |
| dc.date.copyright | 2012-08-28 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-10 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16021 | - |
| dc.description.abstract | 先天免疫系統招募各種穿膜及細胞質中生殖系編碼 (germline-encoded)的模式識別受體(pattern recognition receptors, PRRs) 來偵測外來病原的pathogen-associatedmolecular patterns (PAMPs)，像是脂多醣 (lipopolysaccharide, LPS), 肽聚醣(peptidoglycan, PGN),鞭毛(flagellin), 核酸(DNA) 及CpG DNA. 這些被PAMPs 刺激的受體便會啟動細胞內的訊息傳遞以達到宿主防禦的反應。
當PRRs 的leucine-rich repeat (LRR) 辨認到各種各樣的PAMPs, 細胞質中nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs)的N 端Pyrin domain (PYD) 利用它的homotypic 作用力使訊號傳到下游。PYD-containingNLRs (NLRPs)家族總共有14 個成員，而其中幾個發生突變跟人類發炎失調疾病息息相關。 人類的PYNOD, 亦稱NLRP10 是一個新穎的發炎負向調控者，其特徵是缺乏C端的LRR。通過它的PYD domain, PYNOD抑制ASC (apoptosis-associated speck-like protein containing a CARD)的聚合反應，使capase-1 的活化以及caspase-1 媒介的1L-1β 成熟化受到壓制。由於PYNOD 具有抗發炎性，從結構的角度了解它跟ASC的PYD-PYD 的結合模式是重要的。在本篇論文中，我主要研究PYNOD 的三維核磁共振結構和它的動態，結果顯示其外形是由6 個Helices 構成的桶狀構形，連接H2 和H3 有突出的loop L3。骨架動態數據發現這loop L3 及H3 比其他5 段Helices有相對性較高的彈性。 | zh_TW |
| dc.description.abstract | The innate immune system recruits various transmembrane and cytoplasmic germline-encoded pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMP) motifs of microbial invaders, such as lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, ds-DNA, and CpG DNA. PAMP-activated receptors then trigger intracellular signaling cascades that lead to a spectrum of host defense reactions. While diverse PAMP motifs are recognized by the leucine-rich repeat (LRR) protein modules present in PRRs, the N-terminal pyrin domain (PYD) of
cytoplasmic nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) links PAMP-recognition to downstream signaling cascades through specific homotypic interactions. There are 14 members of PYD-containing NLRs (NLRPs) and mutations in several of them have been implicated in numerous human inflammatory disorders. Human PYNOD/NLRP10 is a novel negative regulator of inflammation characterized by the lack of a C-terminal LRR domain. Via its PYD domain, PYNOD suppresses oligomerization of ASC (apoptosis-associated speck-like protein containing a CARD), a critical PYD-containing signaling adaptor protein, which leads to inhibition of caspase-1 activation and caspase-1 mediated maturation of 1L-1β. Owing to its important anti-inflammatory activity, we have sought to elucidate the structural basis of PYD-mediated interaction of PYNOD with ASC. Here I present the structure and dynamics of the human PYNOD PYD, which shows that PYNOD PYD adopts a core six-helix bundle structure with a prominent loop L3 between helices H2 and H3. Backbone 15N relaxation data revealed this L3 loop and the H3 helix display a greater degree of conformational disorder than the other five helices. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T17:58:20Z (GMT). No. of bitstreams: 1 ntu-101-R99b46035-1.pdf: 3310684 bytes, checksum: 0257203f97adb18b063d7b3dd9171305 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Table of contents
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 TABLES XI LIST OF FIGURES XII Chapter 1 Introduction 1 1.1 Overview 1 1.2 Motivation of research 5 Chapter 2 Materials and Methods 7 2.1 Expression and purification of PYDs 7 2.1.1 Denaturing and refolding of full-length ASC 7 2.1.2 Denaturing and refolding of ASC PYD domain and ASC PYD linker 8 2.1.3 Expression and purification of MBP-ASC 9 2.1.4 Expression and purification of PYNOD PYD domain and PYNOD PYD linker 11 2.1.5 Co-expression of PYNOD PYD and ASC PYD 13 2.1.6 Denaturing and refolding of AIM2 PYD domain 13 2.1.7 Expressing and purification of POP1 14 2.1.8 Expression screening of POP2, PYNOD and AIM2 15 2.2 Circular Dichroism Experiments 16 VII 2.2.1 Introduction 16 2.2.2 Procedures 16 2.3 Nuclear Magnetic Resonance 18 2.3.1 Introduction 18 2.3.2 Torsion angle restraints 19 2.3.3 Chemical shift index 19 2.3.4 Hydrogen bond restraints 20 2.3.5 Residual dipolar coupling 20 2.3.6 Backbone relaxation 21 2.3.6.1 Reduced spectral density mapping 22 2.3.7 Procedures 23 Chapter 3 Results 25 3.1 Expression and purification of PYDs 25 3.1.1 Full-length ASC and MBP-ASC 25 3.1.2 AIM2 PYD, ASC PYD and ASC PYD linker 27 3.1.3 PYNOD PYD and PYNOD PYD linker 28 3.1.4 Coexpression of PYNOD PYD and ASC PYD 28 3.1.5 POP1, POP2, PYNOD and AIM2 28 3.2 CD spectra of PYDs 29 3.3 NMR assignment and structure of PYNOD PYD 30 3.4 Backbone dynamics analysis of PYNOD PYD 31 3.5 Complex formation of PYDs 32 3.5.1 ASC PYD / ASC PYD L25A and PYNOD PYD 32 3.5.2 ASC PYD / ASC PYD L25A and AIM2 PYD 33 3.5.3 ASC PYD / POP1 33 VIII 3.5.4 Complex of other PYDs 33 Chapter 4 Discussions 35 4.1 Structural and dynamics comparison of PYNOD with other PYDs 35 4.2 Electrostatic surface of PYDs 36 4.3 Complex formation of PYDs 36 REFERENCES 78 LIST OF POSTER AND PUBLICATION 83 | |
| dc.language.iso | en | |
| dc.subject | pyrin | zh_TW |
| dc.subject | 核磁共振 | zh_TW |
| dc.subject | PYNOD | zh_TW |
| dc.subject | PYNOD | en |
| dc.subject | pyrin | en |
| dc.subject | NMR | en |
| dc.title | PYRIN domains 的表現，純化及三維核磁共振結構分析 | zh_TW |
| dc.title | Expression, purification and the NMR analysis of PYRIN domains | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張七鳳,林世昌 | |
| dc.subject.keyword | pyrin,核磁共振,PYNOD, | zh_TW |
| dc.subject.keyword | pyrin,NMR,PYNOD, | en |
| dc.relation.page | 81 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2012-08-10 | |
| 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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