Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles.
Proc Natl Acad Sci U S A
; 118(36)2021 09 07.
Article
em En
| MEDLINE
| ID: mdl-34462352
ABSTRACT
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 Aß42 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
/
Amiloide
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article