Molecular dynamics simulations of a fibrillogenic peptide derived from apolipoprotein C-II.
The pathway to amyloid fibril formation in proteins involves specific structural changes leading to the combination of misfolded intermediates into oligomeric assemblies. Recent NMR studies showed the presence of "turns" in amyloid peptides, indicating that turn formation may play an important role in the nucleation of the intramolecular folding and possible assembly of amyloid. Fully solvated all-atom molecular dynamics simulations were used to study the structure and dynamics of the apolipoprotein C-II peptide 56 to 76, associated with the formation of amyloid fibrils. The peptide populated an ensemble of turn structures, stabilized by hydrogen bonds and hydrophobic interactions enabling the formation of a strong hydrophobic core which may provide the conditions required to initiate aggregation. Two competing mechanisms discussed in the literature were observed. This has implications in understanding the mechanism of amyloid formation in not only apoC-II and its fragments, but also in other amyloidogenic peptides.
Legge
F Sue
FS
Applied Physics, School of Applied Sciences, RMIT University, GPO Box 2476V Melbourne, Victoria, 3001, Australia.
Treutlein
Herbert
H
Howlett
Geoffrey J
GJ
Yarovsky
Irene
I
D000682:Amyloid / Q000096:biosynthesis* / Q000648:ultrastructure; D053304:Apolipoprotein C-II / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008055:Lipids / Q000032:analysis; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary