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bioRxiv · 10.1101/2020.09.01.278481

Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles

Koloteva-Levine, N.·Marchante, R.·Purton, T. J.·Hiscock, J. R.·Tuite, M. F.·Xue, W.-F.
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Abstract

Amyloid seeds are nanometre-sized protein particles that accelerate amyloid assembly, as well as propagate and transmit the amyloid protein conformation associated with a wide range of protein misfolding diseases. However, seeded amyloid growth through templated elongation at fibril ends cannot explain the full range of molecular behaviours observed during cross-seeded formation of amyloid by heterologous seeds. Here, we demonstrate that amyloid seeds can accelerate amyloid formation via a surface catalysis mechanism without propagating the specific amyloid conformation associated with the seeds. This type of seeding mechanism is demonstrated through quantitative characterisation of the cross-seeded assembly reactions involving two non-homologous and unrelated proteins: the human A{beta}42 peptide and the yeast prion-forming protein Sup35NM. Our results suggest experimental approaches to differentiate seeding by templated elongation from non-templated amyloid seeding, and rationalise the molecular mechanism of the cross-seeding phenomenon as a manifestation of the aberrant surface activities presented by amyloid seeds as nanoparticles.

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Koloteva-Levine, N., Marchante, R., Purton, T. J., Hiscock, J. R., Tuite, M. F., Xue, W.-F.. 2020-09-03. Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles. https://doi.org/10.1101/2020.09.01.278481

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