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It has attracted multiple interests from clinical study and\u003cbr /\u003efundamental research. Because it is possible that partially denatured protein in amyloid fiblil escapes ftom\u003cbr /\u003ethe cellular quality control and propagates by itself, the amyloid filbril is expected to be dangerous on\u003cbr /\u003e clinical studies of several diseases. Such a character is also in the field of structural biology \u003cbr /\u003ewith regards to self-assembly of macromolecules and protein folding.\u003cbr /\u003e To date,much effort has been paid on the protein structure in an amyloid fibril,because of importance\u003cbr /\u003efor understanding the mechanism of protein folding and fibril formation. However,it is still a challenging\u003cbr /\u003eissue to determine the whole protein structure in the fibril.\u003cbr /\u003e Another approach on this matter is to limit a scope. For example, one of the important aspects of the\u003cbr /\u003efibril is a property to replicate by itself.In this case,a nature of intermolecular interactions would be an\u003cbr /\u003eindispensable information to understand what it is. As another example,it is of\u003cbr /\u003e interest to know why the morphology of amyloid fibril is unique and exhibit similar dimension to each\u003cbr /\u003eother regardless of precursor proteins.In this case,a width of β-sheet core(as a common feature)should be\u003cbr /\u003everified and such a factor should be discussed in relation to the dimension of the aggregation. Thus,partial\u003cbr /\u003echaracter of the structure may give a hint to explain several properties of the amyloid fibril. \u003cbr /\u003e In this thesis, an amyloid fibril of β\u003csmall\u003e2\u003c/small\u003e-microglobulin(β\u003csmall\u003e2\u003c/small\u003em),which is related to the dialysis-related\u003cbr /\u003e amyloidosis,has been treated. IR spectroscopy and IR microscope is adopted as main technique. Truncated\u003cbr /\u003e peptide fragment of b2m is ehosen as a probe to search the structural information of the interacting\u003cbr /\u003esegment.\u003cbr /\u003e My aims at this point. First,a novel procedure is applied to clarify the structure of the interacting\u003cbr /\u003esegment of β\u003csmall\u003e2\u003c/small\u003em amyloid fibril(fA[β\u003csmall\u003e2\u003c/small\u003em])by using IR spectroscopy. Even though the structural information\u003cbr /\u003ebrought from IR spectroscopy is rather obscure than those of others including X-ray\u003cbr /\u003ediffraction or NMR spectroscopy, it brings practically essential information when it is applied in an\u003cbr /\u003eappropriate way.Mechanical structure will be clarified.\u003cbr /\u003e Second aim of my thesis is the elucidation of chemical property of the interacting segment. For this\u003cbr /\u003epurpose,several fragment peptides derived from the sequence of β\u003csmall\u003e2\u003c/small\u003em is examined.fibrilization efficiency\u003cbr /\u003eand the structure are discussed under, various pH conditions,and the experimental results will be discussed\u003cbr /\u003ein terms of the pH dependence of side chains and terminal charges\u003cbr /\u003e This thesis contains four chapters:Chapter 1 reviews the general background of amyloid fibril,\u003cbr /\u003echaracter of β\u003csmall\u003e2\u003c/small\u003em as well as its fibril state,the remaining problems in this field,and the purpose of this\u003cbr /\u003ethesis. Chapter 2 reports the novel protocol to search the position and to explore the conformation of the\u003cbr /\u003einteracting segment along the primary structure of β\u003csmall\u003e2\u003c/small\u003em. In this chapter,the #21-31 fragment of β\u003csmall\u003e2\u003c/small\u003em was\u003cbr /\u003echosen as probe,and its fibril was prepared with the aid of the protein seeding property of the protein fiblil\u003cbr /\u003e(fA[#21-31]-on-fA[β\u003csmall\u003e2\u003c/small\u003em]).The formation of this species was detected by ThT fluorescence method.\u003cbr /\u003ePossibility of spontaneous fibril formation of the #21-31 fragment was eliminated by designing the fibril\u003cbr /\u003e preparation condition adequately. It is considered that attached tip that consists of\u003cbr /\u003ethe flagment peptide molds the structure of the interacting segment of protein fibril. The result confirms\u003cbr /\u003ethat one of the interacting segments is located at F22~V27 region with planar parallelβ-sheet structure.\u003cbr /\u003eThis feature is different from the spontaneous fibril on which the energetically stable structure is\u003cbr /\u003eaccompanied by moderate curl of β-sheet. This difference has been assigned to the planar β-sheet structure\u003cbr /\u003eof the interacting segment of fA [β\u003csmall\u003e2\u003c/small\u003em] and the molding property of the amyloid fibril. Chapter 3 treats\u003cbr /\u003eamyloid formed by truncated peptides of β\u003csmall\u003e2\u003c/small\u003emand consisted of two parts(I and Ⅱ);I focuses on side chain\u003cbr /\u003eeffect on fibril formation and II discusses the terminal charge effect on the structure.Both focuses on the\u003cbr /\u003echemical character of interacting segment and the factors that appears as the critical interaction therein. In\u003cbr /\u003ethis chapter,a series of fragment peptide of β\u003csmall\u003e2\u003c/small\u003em around the interacting segment (e.g.around #21-31 region)\u003cbr /\u003ewas chosen as sample,and the fibril formation property has been examined under various pH conditions.\u003cbr /\u003eThe result has strongly indicated that the F22~V27 part possesses the inherent propensity to from the b-\u003cbr /\u003esheet.In addition,it has been shown that(i)the aromatic-aromatic interaction is important\u003cbr /\u003e(ii)aliphatic-aliphatic interaction is not strong enough,and(iii)electrostatic interaction between charged\u003cbr /\u003eside chains depends upon the sign of charge with regard to the stabilization of fibril structure.Chapter4 is\u003cbr /\u003ethe conclusion drawn out from this thesis.The nature of interacting segment of fA[β\u003csmall\u003e2\u003c/small\u003em]will be discussed \u003cbr /\u003eby talking account of the mechanical and chemical properties deduced from this study.", "subitem_description_type": "Other"}]}, "item_1_description_7": {"attribute_name": "学位記番号", "attribute_value_mlt": [{"subitem_description": "総研大甲第1015号", "subitem_description_type": "Other"}]}, "item_1_select_14": {"attribute_name": "所蔵", "attribute_value_mlt": [{"subitem_select_item": "有"}]}, "item_1_select_8": {"attribute_name": "研究科", "attribute_value_mlt": [{"subitem_select_item": "先導科学研究科"}]}, "item_1_select_9": {"attribute_name": "専攻", "attribute_value_mlt": [{"subitem_select_item": "22 光科学専攻"}]}, "item_1_text_10": {"attribute_name": "学位授与年度", "attribute_value_mlt": [{"subitem_text_value": "2006"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "LU, Ming", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2016-02-17"}], "displaytype": "simple", "download_preview_message": "", "file_order": 0, "filename": "甲1015_要旨.pdf", "filesize": [{"value": "256.0 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 256000.0, "url": {"label": "要旨・審査要旨", "url": "https://ir.soken.ac.jp/record/1251/files/甲1015_要旨.pdf"}, "version_id": "b6e09912-03ff-46be-8c5a-11d462b694fc"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "thesis", "resourceuri": "http://purl.org/coar/resource_type/c_46ec"}]}, "item_title": "Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy"}, {"subitem_title": "Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy", "subitem_title_language": "en"}]}, "item_type_id": "1", "owner": "1", "path": ["24"], "permalink_uri": "https://ir.soken.ac.jp/records/1251", "pubdate": {"attribute_name": "公開日", "attribute_value": "2010-02-22"}, "publish_date": "2010-02-22", "publish_status": "0", "recid": "1251", "relation": {}, "relation_version_is_last": true, "title": ["Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy"], "weko_shared_id": -1}
Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy
https://ir.soken.ac.jp/records/1251
https://ir.soken.ac.jp/records/12513b3344ce-f077-4d6c-8d35-f51a935ff519
名前 / ファイル | ライセンス | アクション |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2010-02-22 | |||||
タイトル | ||||||
タイトル | Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
資源タイプ | thesis | |||||
著者名 |
呂, 明
× 呂, 明 |
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フリガナ |
ルミン
× ルミン |
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著者 |
LU, Ming
× LU, Ming |
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学位授与機関 | ||||||
学位授与機関名 | 総合研究大学院大学 | |||||
学位名 | ||||||
学位名 | 博士(理学) | |||||
学位記番号 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 総研大甲第1015号 | |||||
研究科 | ||||||
値 | 先導科学研究科 | |||||
専攻 | ||||||
値 | 22 光科学専攻 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2006-09-29 | |||||
学位授与年度 | ||||||
2006 | ||||||
要旨 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Amyloid fibril has been found more than one hundred years ago(1854)in relation to several diseases.<br />It is an aggregation of proteins and/or peptides. It has attracted multiple interests from clinical study and<br />fundamental research. Because it is possible that partially denatured protein in amyloid fiblil escapes ftom<br />the cellular quality control and propagates by itself, the amyloid filbril is expected to be dangerous on<br /> clinical studies of several diseases. Such a character is also in the field of structural biology <br />with regards to self-assembly of macromolecules and protein folding.<br /> To date,much effort has been paid on the protein structure in an amyloid fibril,because of importance<br />for understanding the mechanism of protein folding and fibril formation. However,it is still a challenging<br />issue to determine the whole protein structure in the fibril.<br /> Another approach on this matter is to limit a scope. For example, one of the important aspects of the<br />fibril is a property to replicate by itself.In this case,a nature of intermolecular interactions would be an<br />indispensable information to understand what it is. As another example,it is of<br /> interest to know why the morphology of amyloid fibril is unique and exhibit similar dimension to each<br />other regardless of precursor proteins.In this case,a width of β-sheet core(as a common feature)should be<br />verified and such a factor should be discussed in relation to the dimension of the aggregation. Thus,partial<br />character of the structure may give a hint to explain several properties of the amyloid fibril. <br /> In this thesis, an amyloid fibril of β<small>2</small>-microglobulin(β<small>2</small>m),which is related to the dialysis-related<br /> amyloidosis,has been treated. IR spectroscopy and IR microscope is adopted as main technique. Truncated<br /> peptide fragment of b2m is ehosen as a probe to search the structural information of the interacting<br />segment.<br /> My aims at this point. First,a novel procedure is applied to clarify the structure of the interacting<br />segment of β<small>2</small>m amyloid fibril(fA[β<small>2</small>m])by using IR spectroscopy. Even though the structural information<br />brought from IR spectroscopy is rather obscure than those of others including X-ray<br />diffraction or NMR spectroscopy, it brings practically essential information when it is applied in an<br />appropriate way.Mechanical structure will be clarified.<br /> Second aim of my thesis is the elucidation of chemical property of the interacting segment. For this<br />purpose,several fragment peptides derived from the sequence of β<small>2</small>m is examined.fibrilization efficiency<br />and the structure are discussed under, various pH conditions,and the experimental results will be discussed<br />in terms of the pH dependence of side chains and terminal charges<br /> This thesis contains four chapters:Chapter 1 reviews the general background of amyloid fibril,<br />character of β<small>2</small>m as well as its fibril state,the remaining problems in this field,and the purpose of this<br />thesis. Chapter 2 reports the novel protocol to search the position and to explore the conformation of the<br />interacting segment along the primary structure of β<small>2</small>m. In this chapter,the #21-31 fragment of β<small>2</small>m was<br />chosen as probe,and its fibril was prepared with the aid of the protein seeding property of the protein fiblil<br />(fA[#21-31]-on-fA[β<small>2</small>m]).The formation of this species was detected by ThT fluorescence method.<br />Possibility of spontaneous fibril formation of the #21-31 fragment was eliminated by designing the fibril<br /> preparation condition adequately. It is considered that attached tip that consists of<br />the flagment peptide molds the structure of the interacting segment of protein fibril. The result confirms<br />that one of the interacting segments is located at F22~V27 region with planar parallelβ-sheet structure.<br />This feature is different from the spontaneous fibril on which the energetically stable structure is<br />accompanied by moderate curl of β-sheet. This difference has been assigned to the planar β-sheet structure<br />of the interacting segment of fA [β<small>2</small>m] and the molding property of the amyloid fibril. Chapter 3 treats<br />amyloid formed by truncated peptides of β<small>2</small>mand consisted of two parts(I and Ⅱ);I focuses on side chain<br />effect on fibril formation and II discusses the terminal charge effect on the structure.Both focuses on the<br />chemical character of interacting segment and the factors that appears as the critical interaction therein. In<br />this chapter,a series of fragment peptide of β<small>2</small>m around the interacting segment (e.g.around #21-31 region)<br />was chosen as sample,and the fibril formation property has been examined under various pH conditions.<br />The result has strongly indicated that the F22~V27 part possesses the inherent propensity to from the b-<br />sheet.In addition,it has been shown that(i)the aromatic-aromatic interaction is important<br />(ii)aliphatic-aliphatic interaction is not strong enough,and(iii)electrostatic interaction between charged<br />side chains depends upon the sign of charge with regard to the stabilization of fibril structure.Chapter4 is<br />the conclusion drawn out from this thesis.The nature of interacting segment of fA[β<small>2</small>m]will be discussed <br />by talking account of the mechanical and chemical properties deduced from this study. | |||||
所蔵 | ||||||
値 | 有 |