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2006 Fiscal Year Final Research Report Summary

Clarification of amyloid fibrillation mechanism by modulating intraproteinaceous structure

Research Project

Project/Area Number 17570132
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biophysics
Research InstitutionKobe University

Principal Investigator

TACHIBANA Hideki  Kobe University, Fac. Sci., Dept. Biol., Assoc. Prof., 理学部, 助教授 (70126118)

Project Period (FY) 2005 – 2006
KeywordsProtein / Amyloid / Disulfide / Lysozyme / Nucleation / beta-structure / Hydrogen / deuterium-exchange
Research Abstract

1. The amyloid-fibrillation reaction of a lysozyme all-disulfide-deficient variant, 0SS, depends on salt-concentration and pH in such a way that the screening of the protein positive charge facilitates the fibrillation. It conforms to a nucleation-elongation reaction scheme and there exists critical monomer concentrations. A nucleus size varies with varying salt-concentration and pH. The absolute value of the dissociation rate constant of monomeric unit from the end of fibrillar polymer was obtained using a theoretical equation derived for the purpose by taking the length-distribution of fibrils into account. There exists a large, as much as three-orders of magnitude, variation in the fibrillation rate among the four 1SS variants, which collectively have a various kinds of tertiary constraints and intramolecular structures, implying that the N- and C-terminal regions should be apart from each other for efficient protofibril formation. The fibril diameter as obtained from SAXS measureme … More nt differs significantly among the 1SS variants. Moreover, the fibril of a 4SS molecule differs markedly in both morphology and diameter from the fibrils of 0SS and 1SS. Thus, the reaction rate and mechanism of fibrillation are strongly modulated by the kinds and amount of intraprotein structures.
2. By using NMR-detected H/D-exchange the peptide regions protected from the exchange by virtue of structure formation were identified : in the 0SS fibril they are four peptide regions, each spanning seven to nine residues, which coincide with the regions of both high hydrophobicity and beta-propensity While the fibrils of two 1SS species show protected regions similar to those of 0SS fibril, the fibrils of the other 1SS species show different protected regions. Moreover, these protected regions altogether differ from the core region of WT lysozyme fibril. Thus, the kinds and amount of intraprotein structure modulate the peptide regions involved in nucleation and elongation of amyloid fibrillation. Less

  • Research Products

    (9 results)

All 2007 2006 2005

All Journal Article (9 results)

  • [Journal Article] Kinetic Analysis of Amyloid Protofibril Dissociation and Volumetric Properties of the Transition State2007

    • Author(s)
      Abdul Latif, A. R.
    • Journal Title

      Biophysical Journal 92

      Pages: 323-329

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Volumetric Properties of Amyloid Protofibrils of Disulfide-Deficient Hen Lysozyme2006

    • Author(s)
      Tachibana, H.
    • Journal Title

      生物物理 46

      Pages: S115

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Facile formation of amyloid-like fibrils of hen lysozyme disulfide-variants involves the carboxyl-terminal hydrophobic peptide region2006

    • Author(s)
      Tachibana, H.
    • Journal Title

      生物物理 46

      Pages: S322

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Volumetric Properties of Amyloid Protofibrils of Disulfide-Deficient Hen Lysozyme2006

    • Author(s)
      Tachibana, H.
    • Journal Title

      Seibutsu Butsuri 46

      Pages: S115

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Facile formation of amyloid-like fibrils of hen lysozyme disulfide-variants involves the carboxyl-terminal hydrophobic peptide region2006

    • Author(s)
      Tachibana, H.
    • Journal Title

      Seibutsu Butsuri 46

      Pages: S322

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pressure-jump NMR Study of Dissociation and Association of Amyloid Protofibrils2005

    • Author(s)
      Kamatari, Y.
    • Journal Title

      Journal of Molecular Biology 349

      Pages: 916-921

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characterization of Disulfide-Bond Dynamics in Non-Native States of Lysozyme and Its Disulfide Deletion Mutants by NMR2005

    • Author(s)
      Collins, E. S.
    • Journal Title

      ChemBioChem 6

      Pages: 1619-1627

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Separate peptide regions are structured in fibrils of hen lysozyme disulfide-deficient variant2005

    • Author(s)
      Tachibana, H.
    • Journal Title

      生物物理 45

      Pages: S51

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Separate peptide regions are structured in fibrils of hen lysozyme disulfide-deficient variant2005

    • Author(s)
      Tachibana, H.
    • Journal Title

      Seibutsu Butsuri 45

      Pages: S51

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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