8T08

Preholo-Proteasome from Pre1-1 Pre4-1 Double Mutant

Summary for 8T08

• Entry DOI: 10.2210/pdb8t08/pdb
• EMDB information: 40938
• Descriptor: Proteasome subunit alpha type-1, Proteasome subunit beta type-3, Proteasome subunit beta type-4, ... (17 entities in total)
• Functional Keywords: preholo-proteasome, core particle, hydrolase
• Biological source: Saccharomyces cerevisiae S288C; More
• Total number of polymer chains: 34
• Total formula weight: 919935.80

Authors

Walsh Jr., R.M.,Rawson, S.,Schnell, H.,Velez, B.,Hanna, J. (deposition date: 2023-05-31, release date: 2023-09-06, Last modification date: 2024-10-16)

Primary citation

Walsh Jr., R.M.,Rawson, S.,Schnell, H.M.,Velez, B.,Rajakumar, T.,Hanna, J.
Structure of the preholoproteasome reveals late steps in proteasome core particle biogenesis.
Nat.Struct.Mol.Biol., 30:1516-1524, 2023

PubMed Abstract: Assembly of the proteasome's core particle (CP), a barrel-shaped chamber of four stacked rings, requires five chaperones and five subunit propeptides. Fusion of two half-CP precursors yields a complete structure but remains immature until active site maturation. Here, using Saccharomyces cerevisiae, we report a high-resolution cryogenic electron microscopy structure of preholoproteasome, a post-fusion assembly intermediate. Our data reveal how CP midline-spanning interactions induce local changes in structure, facilitating maturation. Unexpectedly, we find that cleavage may not be sufficient for propeptide release, as residual interactions with chaperones such as Ump1 hold them in place. We evaluated previous models proposing that dynamic conformational changes in chaperones drive CP fusion and autocatalytic activation by comparing preholoproteasome to pre-fusion intermediates. Instead, the data suggest a scaffolding role for the chaperones Ump1 and Pba1/Pba2. Our data clarify key aspects of CP assembly, suggest that undiscovered mechanisms exist to explain CP fusion/activation, and have relevance for diseases of defective CP biogenesis.

PubMed: 37653242
DOI: 10.1038/s41594-023-01081-w

Experimental method

ELECTRON MICROSCOPY (3 Å)