Self-Templated Nucleation in Peptide and Protein aggregation

Abstract

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 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 stabilise the disordered assemblies.

4 pages, 3 figures

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Cited by in corpus (19)

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• Control of pathways and yields of protein crystallization through the interplay of nonspecific and specific attractions
• Kinetics of spontaneous filament nucleation via oligomers: insights from theory and simulation
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• Aggregate geometry in amyloid fibril nucleation
• Phase Diagram of alpha-Helical and beta-Sheet Forming Peptides
• From amorphous aggregates to polymer bundles: The role of stiffness on structural phases in polymer aggregation
• Insight into the correlation between lag time and aggregation rate in the kinetics of protein aggregation
• Interplay between folding and assembly of fibril-forming polypeptides
• Phase diagram of self-assembled rigid rods on two-dimensional lattices: Theory and Monte Carlo simulations
• Nonclassical assembly pathways of anisotropic particles
• Sequence dependent aggregation of peptides and fibril formation
• Thermodynamics of amyloid formation and the role of intersheet interactions
• Intrinsic Defect Formation in Peptide Self-Assembly
• Phase behaviour and self-assembly of semiflexible polymers in poor-solvent solutions
• Protein sequence and structure: Is one more fundamental than the other?
• A Two-Step Biopolymer Nucleation Model Shows a Nonequilibrium Critical Point
• Length distribution of stiff, self-assembled polymers at thermal equilibrium
• Templating Aggregation