{"created":"2023-06-20T13:21:08.685228+00:00","id":1251,"links":{},"metadata":{"_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":["2:431:24"]},"author_link":["0","0","0"],"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_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．<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.","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","filename":"甲1015_要旨.pdf","filesize":[{"value":"256.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","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"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1251","relation_version_is_last":true,"title":["Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-06-20T16:06:34.859478+00:00"}