8TM5

Human mixed 13S proteasome assembly intermediate

8TM5 の概要

• エントリーDOI: 10.2210/pdb8tm5/pdb
• EMDBエントリー: 41377 41378 41379
• 分子名称: Proteasome subunit alpha type-2, Proteasome subunit beta type-2, Proteasome assembly chaperone 1, ... (13 entities in total)
• 機能のキーワード: proteasome, proteasome assembly, pomp, beta ring assembly, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 349274.09

構造登録者

Zhang, H.,Zhao, J. (登録日: 2023-07-28, 公開日: 2024-10-23, 最終更新日: 2025-05-14)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3 Å)