{"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．
It is an aggregation of proteins and/or peptides. It has attracted multiple interests from clinical study and
fundamental research. Because it is possible that partially denatured protein in amyloid fiblil escapes ftom
the cellular quality control and propagates by itself, the amyloid filbril is expected to be dangerous on
clinical studies of several diseases. Such a character is also in the field of structural biology
with regards to self-assembly of macromolecules and protein folding.
To date，much effort has been paid on the protein structure in an amyloid fibril，because of importance
for understanding the mechanism of protein folding and fibril formation. However，it is still a challenging
issue to determine the whole protein structure in the fibril．
Another approach on this matter is to limit a scope. For example, one of the important aspects of the
fibril is a property to replicate by itself．In this case，a nature of intermolecular interactions would be an
indispensable information to understand what it is. As another example，it is of
interest to know why the morphology of amyloid fibril is unique and exhibit similar dimension to each
other regardless of precursor proteins．In this case，a width of β-sheet core（as a common feature）should be
verified and such a factor should be discussed in relation to the dimension of the aggregation. Thus，partial
character of the structure may give a hint to explain several properties of the amyloid fibril.
In this thesis, an amyloid fibril of β2-microglobulin(β2m),which is related to the dialysis-related
amyloidosis，has been treated. IR spectroscopy and IR microscope is adopted as main technique. Truncated
peptide fragment of b2m is ehosen as a probe to search the structural information of the interacting
segment.
My aims at this point. First，a novel procedure is applied to clarify the structure of the interacting
segment of β2m amyloid fibril（fA[β2m]）by using IR spectroscopy. Even though the structural information
brought from IR spectroscopy is rather obscure than those of others including X-ray
diffraction or NMR spectroscopy, it brings practically essential information when it is applied in an
appropriate way．Mechanical structure will be clarified．
Second aim of my thesis is the elucidation of chemical property of the interacting segment. For this
purpose，several fragment peptides derived from the sequence of β2m is examined．fibrilization efficiency
and the structure are discussed under, various pH conditions，and the experimental results will be discussed
in terms of the pH dependence of side chains and terminal charges
This thesis contains four chapters：Chapter 1 reviews the general background of amyloid fibril，
character of β2m as well as its fibril state，the remaining problems in this field，and the purpose of this
thesis. Chapter 2 reports the novel protocol to search the position and to explore the conformation of the
interacting segment along the primary structure of β2m. In this chapter，the ＃21-31 fragment of β2m was
chosen as probe，and its fibril was prepared with the aid of the protein seeding property of the protein fiblil
（fA[＃21-31]-on-fA[β2m]）．The formation of this species was detected by ThT fluorescence method．
Possibility of spontaneous fibril formation of the #21-31 fragment was eliminated by designing the fibril
preparation condition adequately. It is considered that attached tip that consists of
the flagment peptide molds the structure of the interacting segment of protein fibril. The result confirms
that one of the interacting segments is located at F22～V27 region with planar parallelβ－sheet structure.
This feature is different from the spontaneous fibril on which the energetically stable structure is
accompanied by moderate curl of β-sheet. This difference has been assigned to the planar β－sheet structure
of the interacting segment of fA [β2m] and the molding property of the amyloid fibril. Chapter 3 treats
amyloid formed by truncated peptides of β2mand consisted of two parts（I and Ⅱ）；I focuses on side chain
effect on fibril formation and II discusses the terminal charge effect on the structure．Both focuses on the
chemical character of interacting segment and the factors that appears as the critical interaction therein. In
this chapter，a series of fragment peptide of β2m around the interacting segment （e．g．around ＃21－31 region）
was chosen as sample，and the fibril formation property has been examined under various pH conditions．
The result has strongly indicated that the F22～V27 part possesses the inherent propensity to from the b-
sheet．In addition，it has been shown that（i）the aromatic-aromatic interaction is important
（ii）aliphatic－aliphatic interaction is not strong enough，and（iii）electrostatic interaction between charged
side chains depends upon the sign of charge with regard to the stabilization of fibril structure．Chapter4 is
the conclusion drawn out from this thesis．The nature of interacting segment of fA［β2m］will be discussed
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"}