Self-templated nucleation in peptide and protein aggregation.
Peptides and proteins exhibit a common tendency to assemble into highly ordered fibrillar aggregates, whose formation proceeds in a nucleation-dependent manner that is often preceded by the formation of oligomeric assemblies. This process has received much attention because disordered oligomeric aggregates have been associated with neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Here we describe a self-templated nucleation mechanism that determines the transition between the initial condensation of polypeptide chains into disordered assemblies and their reordering into fibrillar structures. The results that we present show that at the molecular level this transition is due to the ability of polypeptide chains to reorder within oligomers into fibrillar assemblies whose surfaces act as templates that stabilize the disordered assemblies.
Auer
Stefan
S
Centre for Self Organising Molecular Systems, University of Leeds, Leeds LS2 9JT, United Kingdom. s.auer@leeds.ac.uk
Dobson
Christopher M
CM
Vendruscolo
Michele
M
Maritan
Amos
A
D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D010455:Peptides; D011506:Proteins