8TM4

Human pre 13S proteasome assembly intermediate

Summary for 8TM4

• Entry DOI: 10.2210/pdb8tm4/pdb
• EMDB information: 41377 41378 41379
• Descriptor: Proteasome subunit alpha type-2, Proteasome subunit beta type-2, Proteasome assembly chaperone 1, ... (13 entities in total)
• Functional Keywords: proteasome, proteasome assembly, pomp, beta ring assembly, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 349274.09

Authors

Zhang, H.,Zhao, J. (deposition date: 2023-07-28, release date: 2024-10-23, Last modification date: 2025-05-14)

Primary citation

Zhang, H.,Zhou, C.,Mohammad, Z.,Zhao, J.
Structural basis of human 20S proteasome biogenesis.
Nat Commun, 15:8184-8184, 2024

PubMed Abstract: New proteasomes are produced to accommodate increases in cellular catabolic demand and prevent the accumulation of cytotoxic proteins. Formation of the proteasomal 20S core complex relies on the function of the five chaperones PAC1-4 and POMP. Here, to understand how these chaperones facilitate proteasome assembly, we tagged the endogenous chaperones using CRISPR/Cas gene editing and examined the chaperone-bound complexes by cryo-EM. We observe an early α-ring intermediate subcomplex that is stabilized by PAC1-4, which transitions to β-ring assembly upon dissociation of PAC3/PAC4 and rearrangement of the PAC1 N-terminal tail. Completion of the β-ring and dimerization of half-proteasomes repositions critical lysine K33 to trigger cleavage of the β pro-peptides, leading to the concerted dissociation of POMP and PAC1/PAC2 to yield mature 20S proteasomes. This study reveals structural insights into critical points along the assembly pathway of the human proteasome and provides a molecular blueprint for 20S biogenesis.

PubMed: 39294158
DOI: 10.1038/s41467-024-52513-0

Experimental method

ELECTRON MICROSCOPY (3 Å)