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The mechanism of monomer transfer between two structurally distinct PrP oligomers

Abstract : In mammals, Prion pathology refers to a class of infectious neuropathologies whose mechanism is based on the self-perpetuation of structural information stored in the pathological conformer. The characterisation of the PrP folding landscape has revealed the existence of a plethora of pathways conducing to the formation of structurally different assemblies with different biological properties. However, the biochemical interconnection between these diverse assemblies remains unclear. The PrP oligomerisation process leads to the formation of neurotoxic and soluble assemblies called O1 oligomers with a high size heterodispersity. By combining the measurements in time of size distribution and average size with kinetic models and data assimilation, we revealed the existence of at least two structurally distinct sets of assemblies, termed Oa and Ob, forming O1 assemblies. We propose a kinetic model representing the main processes in prion aggregation pathway: polymerisation, depolymerisation, and disintegration. The two groups interact by exchanging monomers through a disintegration process that increases the size of Oa. Our observations suggest that PrP oligomers constitute a highly dynamic population.
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Submitted on : Sunday, August 13, 2017 - 11:13:42 PM
Last modification on : Thursday, April 9, 2020 - 5:08:18 PM

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Aurora Armiento, Philippe Moireau, Davy Martin, Nad’a Lepejova, Marie Doumic, et al.. The mechanism of monomer transfer between two structurally distinct PrP oligomers. PLoS ONE, Public Library of Science, 2017, 12 (7), ⟨10.1371/journal.pone.0180538⟩. ⟨hal-01574346⟩

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