8U7U

Proteasome 20S Core Particle from Beta 3 D205 deletion

8U7U の概要

• エントリーDOI: 10.2210/pdb8u7u/pdb
• 関連するPDBエントリー: 8U6Y
• EMDBエントリー: 41963 41993
• 分子名称: Proteasome subunit alpha type-5, Proteasome subunit beta type-5, Proteasome subunit alpha type-3, ... (14 entities in total)
• 機能のキーワード: proteasome, core particle, hydrolase
• 由来する生物種: Saccharomyces cerevisiae S288C; 詳細
• タンパク質・核酸の鎖数: 28
• 化学式量合計: 766577.96

構造登録者

Walsh Jr., R.M.,Rawson, S.,Velez, B.,Blickling, M.,Razi, A.,Hanna, J. (登録日: 2023-09-15, 公開日: 2024-04-17, 最終更新日: 2024-09-04)

主引用文献

Velez, B.,Walsh Jr., R.M.,Rawson, S.,Razi, A.,Adams, L.,Perez, E.F.,Jiao, F.,Blickling, M.,Rajakumar, T.,Fung, D.,Huang, L.,Hanna, J.
Mechanism of autocatalytic activation during proteasome assembly.
Nat.Struct.Mol.Biol., 31:1167-1175, 2024

PubMed Abstract: Many large molecular machines are too elaborate to assemble spontaneously and are built through ordered pathways orchestrated by dedicated chaperones. During assembly of the core particle (CP) of the proteasome, where protein degradation occurs, its six active sites are simultaneously activated via cleavage of N-terminal propeptides. Such activation is autocatalytic and coupled to fusion of two half-CP intermediates, which protects cells by preventing activation until enclosure of the active sites within the CP interior. Here we uncover key mechanistic aspects of autocatalytic activation, which proceeds through alignment of the β5 and β2 catalytic triad residues, respectively, with these triads being misaligned before fusion. This mechanism contrasts with most other zymogens, in which catalytic centers are preformed. Our data also clarify the mechanism by which individual subunits can be added in a precise, temporally ordered manner. This work informs two decades-old mysteries in the proteasome field, with broader implications for protease biology and multisubunit complex assembly.

PubMed: 38600323
DOI: 10.1038/s41594-024-01262-1

実験手法

ELECTRON MICROSCOPY (2.16 Å)