Self-Templated Nucleation in Peptide and Protein Aggregation

Stefan Auer, Christopher M. Dobson, Michele Vendruscolo, Amos Maritan
2008 Physical Review Letters  
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 disordered 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 diseases. Here we describe a self-templated nucleation mechanism that determines the
more » ... tion 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 stabilise the disordered assemblies.
doi:10.1103/physrevlett.101.258101 pmid:19113754 fatcat:igg6fw3pl5exbk45z6ccprosp4