9D0T

Proteasome core particle assembly intermediate Blm10:13S purified from Saccharomyces cerevisiae

Summary for 9D0T

• Entry DOI: 10.2210/pdb9d0t/pdb
• EMDB information: 46461
• Descriptor: Proteasome subunit alpha type-1, Proteasome subunit beta type-4, Proteasome activator BLM10, ... (12 entities in total)
• Functional Keywords: proteasome, assembly chaperone, blm10, pa200, blm10-13s, pba1, cp, hydrolase
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 12
• Total formula weight: 540819.58

Authors

Chen, X.,Kaur, M.,Roelofs, J.,Walters, K.J. (deposition date: 2024-08-07, release date: 2024-12-04, Last modification date: 2025-08-20)

Primary citation

Kaur, M.,Chen, X.,Lee, S.Y.,Weaver, T.M.,Freudenthal, B.D.,Walters, K.J.,Roelofs, J.
Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle.
Biorxiv, 2024

PubMed Abstract: Proteasomes are formed by chaperone-assisted assembly of core particles (CPs) and regulatory particles (RPs). The CP chaperone dimer Pba1/Pba2 binds early to proteasome subunits, and is thought to be replaced by Blm10 to form Blm10:CP, which promotes ATP-independent degradation of disordered proteins. Here, we present evidence of distinct parallel assembly pathways for CP by solving five cryo-EM structures including a Blm10:13S pre-assembly intermediate. Our data conflict with the current model of Blm10 and Pba1/Pba2 sequential activity in a single assembly pathway, as we find their CP binding is mutually exclusive and both are present on early and late assembly intermediates. CP affinity for Pba1/Pba2 is reduced during maturation, promoting Pba1/Pba2 release. We find Blm10 undergoes no such affinity switch, suggesting this pathway predominantly yields mature Blm10-bound CP. Altogether, our findings conflict with the current paradigm of sequential CP binding to instead indicate parallel assembly pathways by Pba1/Pba2 and Blm10.

PubMed: 39574619
DOI: 10.1101/2024.11.04.621988

Experimental method

ELECTRON MICROSCOPY (2.84 Å)