Heterotypic Amyloid ß interactions facilitate amyloid assembly and modify amyloid structure.
EMBO J
; 41(2): e108591, 2022 12 17.
Article
em En
| MEDLINE
| ID: mdl-34842295
ABSTRACT
It is still unclear why pathological amyloid deposition initiates in specific brain regions or why some cells or tissues are more susceptible than others. Amyloid deposition is determined by the self-assembly of short protein segments called aggregation-prone regions (APRs) that favour cross-ß structure. Here, we investigated whether Aß amyloid assembly can be modified by heterotypic interactions between Aß APRs and short homologous segments in otherwise unrelated human proteins. Mining existing proteomics data of Aß plaques from AD patients revealed an enrichment in proteins that harbour such homologous sequences to the Aß APRs, suggesting heterotypic amyloid interactions may occur in patients. We identified homologous APRs from such proteins and show that they can modify Aß assembly kinetics, fibril morphology and deposition pattern in vitro. Moreover, we found three of these proteins upon transient expression in an Aß reporter cell line promote Aß amyloid aggregation. Strikingly, we did not find a bias towards heterotypic interactions in plaques from AD mouse models where Aß self-aggregation is observed. Based on these data, we propose that heterotypic APR interactions may play a hitherto unrealized role in amyloid-deposition diseases.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
/
Proteoma
/
Mapas de Interação de Proteínas
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2022
Tipo de documento:
Article