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Title | The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 6173, Year 2021 |
Publish date | Oct 26, 2021 |
Authors | Indrajit Sahu / Sachitanand M Mali / Prasad Sulkshane / Cong Xu / Andrey Rozenberg / Roni Morag / Manisha Priyadarsini Sahoo / Sumeet K Singh / Zhanyu Ding / Yifan Wang / Sharleen Day / Yao Cong / Oded Kleifeld / Ashraf Brik / Michael H Glickman / |
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, ...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. |
External links | Nat Commun / PubMed:34702852 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.22 - 4.47 Å |
Structure data | EMDB-13389: human 20S proteasome (before post-processing) EMDB-31724, PDB-7v5g: EMDB-31727, PDB-7v5m: EMDB-31728: EMDB-31730: |
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Keywords | HYDROLASE / 20S proteasome / human / substrate / ubiquitin |