6WJN

SD-like state of human 26S Proteasome with non-cleavable M1-linked hexaubiquitin and E3 ubiquitin ligase E6AP/UBE3A

Summary for 6WJN

• Entry DOI: 10.2210/pdb6wjn/pdb
• Related: 5VFR
• EMDB information: 21691 21696 21697 21698 21699 21700
• Descriptor: 26S proteasome non-ATPase regulatory subunit 1, 26S proteasome non-ATPase regulatory subunit 8, 26S proteasome complex subunit SEM1, ... (34 entities in total)
• Functional Keywords: 26s protease, ubiquitin, complex, subunit, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 46
• Total formula weight: 1522353.54

Authors

Chen, X.,Walters, K.J. (deposition date: 2020-04-14, release date: 2020-08-05, Last modification date: 2024-03-06)

Primary citation

Chen, X.,Dorris, Z.,Shi, D.,Huang, R.K.,Khant, H.,Fox, T.,de Val, N.,Williams, D.,Zhang, P.,Walters, K.J.
Cryo-EM Reveals Unanchored M1-Ubiquitin Chain Binding at hRpn11 of the 26S Proteasome.
Structure, 28:1206-1217.e4, 2020

PubMed Abstract: The 26S proteasome is specialized for regulated protein degradation and formed by a dynamic regulatory particle (RP) that caps a hollow cylindrical core particle (CP) where substrates are proteolyzed. Its diverse substrates unify as proteasome targets by ubiquitination. We used cryogenic electron microscopy (cryo-EM) to study how human 26S proteasome interacts with M1-linked hexaubiquitin (M1-Ub) unanchored to a substrate and E3 ubiquitin ligase E6AP/UBE3A. Proteasome structures are available with model substrates extending through the RP ATPase ring and substrate-conjugated K63-linked ubiquitin chains present at inhibited deubiquitinating enzyme hRpn11 and the nearby ATPase hRpt4/hRpt5 coiled coil. In this study, we find M1-Ub at the hRpn11 site despite the absence of conjugated substrate, indicating that ubiquitin binding at this location does not require substrate interaction with the RP. Moreover, unanchored M1-Ub binds to this hRpn11 site of the proteasome with the CP gating residues in both the closed and opened conformational states.

PubMed: 32783951
DOI: 10.1016/j.str.2020.07.011

Experimental method

ELECTRON MICROSCOPY (5.7 Å)