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  1. 020 学位論文
  2. 先導科学研究科
  3. 22 光科学専攻

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/1251
3b3344ce-f077-4d6c-8d35-f51a935ff519
名前 / ファイル ライセンス アクション
甲1015_要旨.pdf 要旨・審査要旨 (256.0 kB)
Item type 学位論文 / Thesis or Dissertation(1)
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
タイトル Structural Studies of Amyloid Fibril of β2-Microglobulin: Application of IR Micro-spectroscopy
言語 en
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

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呂, 明

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フリガナ ルミン

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ルミン

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著者 LU, Ming

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en 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
値 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.
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