8K0G
Cryo-EM structure of human 26S RP (Ed state) bound to K11/K48-branched ubiquitin (Ub) chain composed of four Ub.
Summary for 8K0G
| Entry DOI | 10.2210/pdb8k0g/pdb |
| EMDB information | 36764 |
| Descriptor | 26S protease regulatory subunit 7, Proteasome subunit alpha type-5, Proteasome subunit alpha type-1, ... (30 entities in total) |
| Functional Keywords | protein degradation, macromolecular complex, ubiquitin-proteasome system, cytosolic protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 30 |
| Total formula weight | 1142301.88 |
| Authors | Hsu, S.T.D.,Draczkowski, P.,Wang, Y.S. (deposition date: 2023-07-09, release date: 2025-01-22, Last modification date: 2025-11-05) |
| Primary citation | Draczkowski, P.,Chen, S.N.,Chen, T.,Wang, Y.S.,Shih, H.A.,Huang, J.Y.C.,Tsai, M.C.,Lin, S.Y.,Lin, S.,Viner, R.,Chang, Y.C.,Wu, K.P.,Hsu, S.D. Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome. Nat Commun, 16:9094-9094, 2025 Cited by PubMed Abstract: Beyond the canonical K48-linked homotypic polyubiquitination for proteasome-targeted proteolysis, K11/K48-branched ubiquitin (Ub) chains are involved in fast-tracking protein turnover during cell cycle progression and proteotoxic stress. Here, we report cryo-EM structures of human 26S proteasome in a complex with a K11/K48-branched Ub chain. The structures revealed a multivalent substrate recognition mechanism involving a hitherto unknown K11-linked Ub binding site at the groove formed by RPN2 and RPN10 in addition to the canonical K48-linkage binding site formed by RPN10 and RPT4/5 coiled-coil. Additionally, RPN2 recognizes an alternating K11-K48-linkage through a conserved motif similar to the K48-specific T1 binding site of RPN1. The insights gleaned from these structures explain the molecular mechanism underlying the recognition of the K11/K48-branched Ub as a priority signal in the ubiquitin-mediated proteasomal degradation. PubMed: 41093839DOI: 10.1038/s41467-025-64719-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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