Structural Characterization of Cardiac Ex Vivo Transthyretin Amyloid: Insight into the Transthyretin Misfolding Pathway In Vivo.
Biochemistry
; 59(19): 1800-1803, 2020 05 19.
Article
en En
| MEDLINE
| ID: mdl-32338497
ABSTRACT
Structural characterization of misfolded protein aggregates is essential to understanding the molecular mechanism of protein aggregation associated with various protein misfolding disorders. Here, we report structural analyses of ex vivo transthyretin aggregates extracted from human cardiac tissue. Comparative structural analyses of in vitro and ex vivo transthyretin aggregates using various biophysical techniques revealed that cardiac transthyretin amyloid has structural features similar to those of in vitro transthyretin amyloid. Our solid-state nuclear magnetic resonance studies showed that in vitro amyloid contains extensive nativelike ß-sheet structures, while other loop regions including helical structures are disrupted in the amyloid state. These results suggest that transthyretin undergoes a common misfolding and aggregation transition to nativelike aggregation-prone monomers that self-assemble into amyloid precipitates in vitro and in vivo.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Prealbúmina
/
Pliegue de Proteína
/
Miocitos Cardíacos
/
Agregado de Proteínas
/
Amiloide
Límite:
Humans
Idioma:
En
Revista:
Biochemistry
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos