SRCP1 Conveys Resistance to Polyglutamine Aggregation.
Mol Cell
; 71(2): 216-228.e7, 2018 07 19.
Article
em En
| MEDLINE
| ID: mdl-30029002
ABSTRACT
The polyglutamine (polyQ) diseases are a group of nine neurodegenerative diseases caused by the expansion of a polyQ tract that results in protein aggregation. Unlike other model organisms, Dictyostelium discoideum is a proteostatic outlier, naturally encoding long polyQ tracts yet resistant to polyQ aggregation. Here we identify serine-rich chaperone protein 1 (SRCP1) as a molecular chaperone that is necessary and sufficient to suppress polyQ aggregation. SRCP1 inhibits aggregation of polyQ-expanded proteins, allowing for their degradation via the proteasome, where SRCP1 is also degraded. SRCP1's C-terminal domain is essential for its activity in cells, and peptides that mimic this domain suppress polyQ aggregation in vitro. Together our results identify a novel type of molecular chaperone and reveal how nature has dealt with the problem of polyQ aggregation.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Chaperonas Moleculares
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos