Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates

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dc.creatorAuer, Stefan
dc.creatorMeersman, Filip
dc.creatorDobson, Christopher M.
dc.creatorVendruscolo, Michele
dc.date2009-01-13
dc.date2009-01-14
dc.date.accessioned2026-07-07T12:29:02Z
dc.date.available2026-07-07T12:29:02Z
dc.descriptionThe presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.
dc.description14 pages, 4 figures
dc.identifierhttps://arxiv.org/abs/0901.1851
dc.identifierhttp://arxiv.org/abs/0901.1851
dc.identifierPLoS Comput Biol 4(11): e1000222 (2008)
dc.identifierdoi:10.1371/journal.pcbi.1000222
dc.identifier.urihttp://salesiana.dossiersoluciones.com/handle/123456789/215742
dc.subjectBiomolecules
dc.titleGeneric Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates
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