Structures of chaperone-associated assembly intermediates reveal coordinated mechanisms of proteasome biogenesis.
Nat Struct Mol Biol
; 28(5): 418-425, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33846632
ABSTRACT
The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an α7ß7ß7α7 configuration. CP biogenesis proceeds through an ordered multistep pathway requiring five chaperones, Pba1-4 and Ump1. Using Saccharomyces cerevisiae, we report high-resolution structures of CP assembly intermediates by cryogenic-electron microscopy. The first structure corresponds to the 13S particle, which consists of a complete α-ring, partial ß-ring (ß2-4), Ump1 and Pba1/2. The second structure contains two additional subunits (ß5-6) and represents a later pre-15S intermediate. These structures reveal the architecture and positions of Ump1 and ß2/ß5 propeptides, with important implications for their functions. Unexpectedly, Pba1's N terminus extends through an open CP pore, accessing the CP interior to contact Ump1 and the ß5 propeptide. These results reveal how the coordinated activity of Ump1, Pba1 and the active site propeptides orchestrate key aspects of CP assembly.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Chaperonas Moleculares
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Proteínas de Saccharomyces cerevisiae
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Complejo de la Endopetidasa Proteasomal
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
Nat Struct Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos