Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles
| Autor: | Jennifer R. Hiscock, Ricardo Marchante, Mick F. Tuite, Liam D. Aubrey, Wei-Feng Xue, Nadejda Koloteva-Levine, Tracey J Purton |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Amyloid
Surface Properties Saccharomyces cerevisiae Heterologous Nanoparticle Amyloidogenic Proteins Peptide Fibril Catalysis Prion Proteins mental disorders Humans protein aggregation and assembly amyloid β peptide chemistry.chemical_classification atomic force microscopy Multidisciplinary biology food and beverages Biological Sciences biology.organism_classification Yeast Biophysics and Computational Biology chemistry Sup35 yeast prion protein Biophysics Nanoparticles Seeding Elongation |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 0027-8424 |
| Popis: | Significance The formation of disease-associated fibrillar amyloid structures can be accelerated by preformed amyloid seeds. This seeding process is thought to occur solely through elongation at amyloid fibril ends, resulting in the templated propagation of the protein conformation encoded in the seeds. We demonstrate that amyloid seeding does not always proceed through templated elongation and show that amyloid seeds are nanoparticles that can accelerate the formation of new heterologous amyloid without templating the protein conformation encoded in the seeds. We provide experimentally testable criteria to distinguish seeding through a templated elongation mechanism from surface catalysis and present mechanistic insights into the amyloid seeding and cross-seeding phenomenon. These findings have wide implications for our understanding of the molecular basis of amyloid cross-interactions. Amyloid seeds are nanometer-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 behaviors 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 characterization of the cross-seeded assembly reactions involving two nonhomologous and unrelated proteins: the human Aβ42 peptide and the yeast prion–forming protein Sup35NM. Our results demonstrate experimental approaches to differentiate seeding by templated elongation from nontemplated amyloid seeding and rationalize the molecular mechanism of the cross-seeding phenomenon as a manifestation of the aberrant surface activities presented by amyloid seeds as nanoparticles. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|