Hydrophobic Peptide Segments in Soluble Proteins Competent For Membrane Insertion: Role in Amyloidogenesis

  • Fiona Cunningham
  • Arianna Rath
  • Charles M Deber
Part of the Advances in Experimental Medicine and Biology book series (volume 611)


Amyloid diseases such as Alzheimer's have a significant impact on human health. While the proteins implicated in these diseases vary in structure, function and cellular location, they share a common pathological mechanism characterized by the formation of amyloid fibrils with a similar morphology [1]. Fibril formation is initiated when a soluble protein misfolds from its native conformation; usually from an a-helix to a β-strand. As well, it has been suggested that regions in soluble proteins prone to amyloidogenesis may have unstable native secondary structure due to a large number of hydrophobic residues with aqueous β-strand propensity [2, 3].

It has been shown that amyloidogenic segments such as the Aβ(1–40) peptide can exhibit characteristics similar to TM segments such as insertion and adoption of α-helical structures in membrane mimetic environments [4]. Because fibrils can be formed from almost any protein, recognition of the factors influencing protein...


Circular Dichroism Membrane Insertion Protein Conformation Change Amyloidogenic Region Apolar Environment 
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Funded, in part, by a grant to CMD from the Canadian Institutes of Health Research (CIHR). FC and AR hold awards from the CIHR Strategic Training Programs.


  1. 1.
    Dobson, C. M. Nature. 426, 884–90 (2003)CrossRefGoogle Scholar
  2. 2.
    Kallberg, Y., et al. J Biol Chem. 276, 12945–50 (2001)CrossRefGoogle Scholar
  3. 3.
    Yoon, S. and Welsh, W. J. Protein Sci. 13, 2149–60 (2004)CrossRefGoogle Scholar
  4. 4.
    Bokvist, M., et al. J Mol Biol. 335, 1039–49 (2004)CrossRefGoogle Scholar
  5. 5.
    Wang, C., Liu, L. P., Deber, C.M. Proc. Am. Pept. Symp. 19, 367–369 (2000)Google Scholar
  6. 6.
    Deber, C. M., et al. Protein Sci. 10, 212–9 (2001)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Fiona Cunningham
    • 1
    • 2
  • Arianna Rath
    • 1
  • Charles M Deber
    • 1
    • 2
  1. 1.Division of Molecular Structure & Function, Research InstituteHospital for Sick ChildrenTorontoCanada
  2. 2.Department of BiochemistryUniversity of TorontoTorontoCanada

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