6U19
Solution Structure of the RAZUL domain from 26S proteasome subunit hRpn10/S5a complexed with the AZUL domain from E3 ligase E6AP/UBE3A
Summary for 6U19
| Entry DOI | 10.2210/pdb6u19/pdb |
| Related | 2KR1 |
| NMR Information | BMRB: 27875 |
| Descriptor | 26S proteasome non-ATPase regulatory subunit 4, Ubiquitin-protein ligase E3A, ZINC ION (3 entities in total) |
| Functional Keywords | proteasome, subunit, complex, ubiquitination, structural protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 15245.32 |
| Authors | Chen, X.,Walters, K.J. (deposition date: 2019-08-15, release date: 2020-03-18, Last modification date: 2024-05-22) |
| Primary citation | Buel, G.R.,Chen, X.,Chari, R.,O'Neill, M.J.,Ebelle, D.L.,Jenkins, C.,Sridharan, V.,Tarasov, S.G.,Tarasova, N.I.,Andresson, T.,Walters, K.J. Structure of E3 ligase E6AP with a proteasome-binding site provided by substrate receptor hRpn10. Nat Commun, 11:1291-1291, 2020 Cited by PubMed Abstract: Regulated proteolysis by proteasomes involves ~800 enzymes for substrate modification with ubiquitin, including ~600 E3 ligases. We report here that E6AP/UBE3A is distinguished from other E3 ligases by having a 12 nM binding site at the proteasome contributed by substrate receptor hRpn10/PSMD4/S5a. Intrinsically disordered by itself, and previously uncharacterized, the E6AP-binding domain in hRpn10 locks into a well-defined helical structure to form an intermolecular 4-helix bundle with the E6AP AZUL, which is unique to this E3. We thus name the hRpn10 AZUL-binding domain RAZUL. We further find in human cells that loss of RAZUL by CRISPR-based gene editing leads to loss of E6AP at proteasomes. Moreover, proteasome-associated ubiquitin is reduced following E6AP knockdown or displacement from proteasomes, suggesting that E6AP ubiquitinates substrates at or for the proteasome. Altogether, our findings indicate E6AP to be a privileged E3 for the proteasome, with a dedicated, high affinity binding site contributed by hRpn10. PubMed: 32157086DOI: 10.1038/s41467-020-15073-7 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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