9HPI
Cryo-EM structure of DDB1dB-CRBN-MRT-0031619, conformation 1
This is a non-PDB format compatible entry.
Summary for 9HPI
| Entry DOI | 10.2210/pdb9hpi/pdb |
| Related | 9HPJ |
| EMDB information | 52330 |
| Descriptor | DNA damage-binding protein 1, Protein cereblon, ZINC ION, ... (4 entities in total) |
| Functional Keywords | targeted protein degradation, molecular glue, ubiquitin proteasome system, crbn, ubiquitin ligase, ligase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 186949.38 |
| Authors | Langousis, G.,Hunkeler, M.,Chami, M.,Quan, C.,Townson, S.,Bonenfant, D. (deposition date: 2024-12-13, release date: 2025-12-03) |
| Primary citation | Langousis, G.,Gainza, P.,Hunkeler, M.,Kapsitidou, D.,Donckele, E.J.,Annunziato, S.,Wiedmer, L.,Jones, K.F.M.,DeMarco, B.,Quan, C.,Bunker, R.D.,Lumb, K.J.,Fasching, B.,Castle, J.C.,Townson, S.A.,Bonenfant, D. A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation. Nat Commun, 16:10157-10157, 2025 Cited by PubMed Abstract: Cereblon (CRBN) is an E3 ubiquitin ligase widely harnessed for targeted protein degradation (TPD). We report the discovery of a molecular glue degrader (MGD), MRT-31619, that drives homo-dimerization of CRBN and promotes its fast, potent, and selective degradation by the ubiquitin proteasome system. Interestingly, the cryo-electron microscopy (cryo-EM) structure of the CRBN homodimer reveals a unique mechanism whereby two molecular glues assemble into a helix-like structure and drive ternary complex formation by mimicking a neosubstrate G-loop degron. This CRBN chemical knockout offers a valuable tool to elucidate the molecular mechanism of MGDs, to investigate its endogenous substrates and understand their physiological roles. PubMed: 41258141DOI: 10.1038/s41467-025-65094-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.93 Å) |
Structure validation
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