Hydrophobic Peptide Segments in Soluble Proteins Competent For Membrane Insertion: Role in Amyloidogenesis
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 . 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 . Because fibrils can be formed from almost any protein, recognition of the factors influencing protein...
KeywordsCircular Dichroism Membrane Insertion Protein Conformation Change Amyloidogenic Region Apolar Environment
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.
- 5.Wang, C., Liu, L. P., Deber, C.M. Proc. Am. Pept. Symp. 19, 367–369 (2000)Google Scholar