7PG9

human 20S proteasome

Summary for 7PG9

• Entry DOI: 10.2210/pdb7pg9/pdb
• EMDB information: 13389
• Descriptor: Proteasome subunit alpha type-6, Proteasome subunit beta type-3, Proteasome subunit beta type-2, ... (14 entities in total)
• Functional Keywords: 20s proteasome, human, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 28
• Total formula weight: 717751.33

Authors

Xu, C.,Cong, Y. (deposition date: 2021-08-13, release date: 2021-10-20, Last modification date: 2024-07-17)

Primary citation

Sahu, I.,Mali, S.M.,Sulkshane, P.,Xu, C.,Rozenberg, A.,Morag, R.,Sahoo, M.P.,Singh, S.K.,Ding, Z.,Wang, Y.,Day, S.,Cong, Y.,Kleifeld, O.,Brik, A.,Glickman, M.H.
The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.
Nat Commun, 12:6173-6173, 2021

PubMed Abstract: The proteasome, the primary protease for ubiquitin-dependent proteolysis in eukaryotes, is usually found as a mixture of 30S, 26S, and 20S complexes. These complexes have common catalytic sites, which makes it challenging to determine their distinctive roles in intracellular proteolysis. Here, we chemically synthesize a panel of homogenous ubiquitinated proteins, and use them to compare 20S and 26S proteasomes with respect to substrate selection and peptide-product generation. We show that 20S proteasomes can degrade the ubiquitin tag along with the conjugated substrate. Ubiquitin remnants on branched peptide products identified by LC-MS/MS, and flexibility in the 20S gate observed by cryo-EM, reflect the ability of the 20S proteasome to proteolyze an isopeptide-linked ubiquitin-conjugate. Peptidomics identifies proteasome-trapped ubiquitin-derived peptides and peptides of potential 20S substrates in Hi20S cells, hypoxic cells, and human failing-heart. Moreover, elevated levels of 20S proteasomes appear to contribute to cell survival under stress associated with damaged proteins.

PubMed: 34702852
DOI: 10.1038/s41467-021-26427-0

Experimental method

ELECTRON MICROSCOPY (3.7 Å)