Pathway of Actin Folding Directed by the Eukaryotic Chaperonin TRiC.
Cell
; 174(6): 1507-1521.e16, 2018 09 06.
Article
en En
| MEDLINE
| ID: mdl-30100183
ABSTRACT
The hetero-oligomeric chaperonin of eukarya, TRiC, is required to fold the cytoskeletal protein actin. The simpler bacterial chaperonin system, GroEL/GroES, is unable to mediate actin folding. Here, we use spectroscopic and structural techniques to determine how TRiC promotes the conformational progression of actin to the native state. We find that actin fails to fold spontaneously even in the absence of aggregation but populates a kinetically trapped, conformationally dynamic state. Binding of this frustrated intermediate to TRiC specifies an extended topology of actin with native-like secondary structure. In contrast, GroEL stabilizes bound actin in an unfolded state. ATP binding to TRiC effects an asymmetric conformational change in the chaperonin ring. This step induces the partial release of actin, priming it for folding upon complete release into the chaperonin cavity, mediated by ATP hydrolysis. Our results reveal how the unique features of TRiC direct the folding pathway of an obligate eukaryotic substrate.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Actinas
/
Chaperonina 60
/
Chaperonina 10
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania