{"_buckets": {"deposit": "e93c54b9-d5ef-4ab3-8b3d-6f3a8a09e216"}, "_deposit": {"created_by": 1, "id": "1251", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "1251"}, "status": "published"}, "_oai": {"id": "oai:ir.soken.ac.jp:00001251", "sets": ["24"]}, "author_link": ["0", "0", "0"], "item_1_biblio_info_21": {"attribute_name": "書誌情報（ソート用）", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2006-09-29", "bibliographicIssueDateType": "Issued"}, "bibliographic_titles": [{}]}]}, "item_1_creator_2": {"attribute_name": "著者名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "呂, 明"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_3": {"attribute_name": "フリガナ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "ルミン"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_date_granted_11": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2006-09-29"}]}, "item_1_degree_grantor_5": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "総合研究大学院大学"}]}]}, "item_1_degree_name_6": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（理学）"}]}, "item_1_description_1": {"attribute_name": "ID", "attribute_value_mlt": [{"subitem_description": "2006535", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "要旨", "attribute_value_mlt": [{"subitem_description": "Amyloid fibril has been found more than one hundred years ago（1854）in relation to several diseases．\u003cbr /\u003eIt is an aggregation of proteins and/or peptides.  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}