5T0J

Structural basis for dynamic regulation of the human 26S proteasome

5T0J の概要

• エントリーDOI: 10.2210/pdb5t0j/pdb
• 関連するPDBエントリー: 5T0C 5T0G 5T0H 5T0I
• EMDBエントリー: 8332 8333 8334 8335 8336 8337
• 分子名称: 26S proteasome non-ATPase regulatory subunit 2, Proteasome subunit beta type-7, Proteasome subunit beta type-3, ... (34 entities in total)
• 機能のキーワード: ubiquitin-proteasome system, aaa-atpase, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q99436 P49720 P49721 P28074 P20618 P28070 P35998 P62191 P43686 P60900 P17980 P62195 P25787 P25789 O14818 P28066 P25786 P25788 P28072; Nucleus : O00231
• タンパク質・核酸の鎖数: 32
• 化学式量合計: 1265686.80

構造登録者

Chen, S.,Wu, J.,Lu, Y.,Ma, Y.B.,Lee, B.H.,Yu, Z.,Ouyang, Q.,Finley, D.,Kirschner, M.W.,Mao, Y. (登録日: 2016-08-16, 公開日: 2016-10-19, 最終更新日: 2024-10-30)

主引用文献

Chen, S.,Wu, J.,Lu, Y.,Ma, Y.B.,Lee, B.H.,Yu, Z.,Ouyang, Q.,Finley, D.J.,Kirschner, M.W.,Mao, Y.
Structural basis for dynamic regulation of the human 26S proteasome.
Proc.Natl.Acad.Sci.USA, 113:12991-12996, 2016

PubMed Abstract: The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states. The substrate-unfolding AAA-ATPase channel is narrowed by 10 inward-facing pore loops arranged into two helices that run in parallel with each other, one hydrophobic in character and the other highly charged. The gate of the core particle was unexpectedly found closed in the ground state and open in only one of the alternative states. Coordinated, stepwise conformational changes of the regulatory particle couple ATP hydrolysis to substrate translocation and regulate gating of the core particle, leading to processive degradation.

PubMed: 27791164
DOI: 10.1073/pnas.1614614113

実験手法

ELECTRON MICROSCOPY (8 Å)