7DRW

Bovine 20S immunoproteasome in complex with two human PA28alpha-beta activators

7DRW の概要

• エントリーDOI: 10.2210/pdb7drw/pdb
• EMDBエントリー: 30828
• 分子名称: Proteasome subunit alpha type-6, Proteasome subunit beta type-3, Proteasome subunit beta type-2, ... (16 entities in total)
• 機能のキーワード: proteasome, immunoproteasome, bovine spleen, pa28, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 42
• 化学式量合計: 1153410.70

構造登録者

Cong, Y.,Xu, C. (登録日: 2020-12-29, 公開日: 2021-01-20, 最終更新日: 2024-03-27)

主引用文献

Chen, J.,Wang, Y.,Xu, C.,Chen, K.,Zhao, Q.,Wang, S.,Yin, Y.,Peng, C.,Ding, Z.,Cong, Y.
Cryo-EM of mammalian PA28 alpha beta-iCP immunoproteasome reveals a distinct mechanism of proteasome activation by PA28 alpha beta.
Nat Commun, 12:739-739, 2021

PubMed Abstract: The proteasome activator PA28αβ affects MHC class I antigen presentation by associating with immunoproteasome core particles (iCPs). However, due to the lack of a mammalian PA28αβ-iCP structure, how PA28αβ regulates proteasome remains elusive. Here we present the complete architectures of the mammalian PA28αβ-iCP immunoproteasome and free iCP at near atomic-resolution by cryo-EM, and determine the spatial arrangement between PA28αβ and iCP through XL-MS. Our structures reveal a slight leaning of PA28αβ towards the α3-α4 side of iCP, disturbing the allosteric network of the gatekeeper α2/3/4 subunits, resulting in a partial open iCP gate. We find that the binding and activation mechanism of iCP by PA28αβ is distinct from those of constitutive CP by the homoheptameric TbPA26 or PfPA28. Our study sheds lights on the mechanism of enzymatic activity stimulation of immunoproteasome and suggests that PA28αβ-iCP has experienced profound remodeling during evolution to achieve its current level of function in immune response.

PubMed: 33531497
DOI: 10.1038/s41467-021-21028-3

実験手法

ELECTRON MICROSCOPY (4.2 Å)