EMD-23503
Cryo-EM structure of Pre-15S proteasome core particle assembly intermediate purified from Pre3-1 proteasome mutant (G34D)
EMD-23503
Single-particle3.17 Å
Deposition: 17/02/2021
Map released: 14/04/2021
Last modified: 06/03/2024
Sample Organism:
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Sample: Pre-15S
Fitted models: 7ls6 (Avg. Q-score: 0.49)
Deposition Authors: Schnell HM , Walsh Jr RM
Sample: Pre-15S
Fitted models: 7ls6 (Avg. Q-score: 0.49)
Deposition Authors: Schnell HM , Walsh Jr RM
Structures of chaperone-associated assembly intermediates reveal coordinated mechanisms of proteasome biogenesis.
Schnell HM ,
Walsh Jr RM ,
Rawson S ,
Kaur M,
Bhanu MK,
Tian G,
Prado MA ,
Guerra-Moreno A ,
Paulo JA ,
Gygi SP ,
Roelofs J ,
Finley D,
Hanna J
(2021) Nat Struct Mol Biol , 28 , 418 - 425
(2021) Nat Struct Mol Biol , 28 , 418 - 425
Abstract:
The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an α7β7β7α7 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 β-ring (β2-4), Ump1 and Pba1/2. The second structure contains two additional subunits (β5-6) and represents a later pre-15S intermediate. These structures reveal the architecture and positions of Ump1 and β2/β5 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 β5 propeptide. These results reveal how the coordinated activity of Ump1, Pba1 and the active site propeptides orchestrate key aspects of CP assembly.
The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an α7β7β7α7 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 β-ring (β2-4), Ump1 and Pba1/2. The second structure contains two additional subunits (β5-6) and represents a later pre-15S intermediate. These structures reveal the architecture and positions of Ump1 and β2/β5 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 β5 propeptide. These results reveal how the coordinated activity of Ump1, Pba1 and the active site propeptides orchestrate key aspects of CP assembly.