9BJZ
Structure of the human DDD-Ube2e2 complex
Summary for 9BJZ
| Entry DOI | 10.2210/pdb9bjz/pdb |
| EMDB information | 44638 |
| Descriptor | DNA damage-binding protein 1, DET1 homolog, DET1- and DDB1-associated protein 1, ... (4 entities in total) |
| Functional Keywords | ddb1, dda1, det1, dcaf, ubiquitin conjugating enzyme, protein binding |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 199448.62 |
| Authors | Loughran, T.,Turk, L.S.,Brown, S.H.J.,Mace, P.D. (deposition date: 2024-04-26, release date: 2025-03-05, Last modification date: 2025-03-12) |
| Primary citation | Burgess, A.E.,Loughran, T.A.,Turk, L.S.,Nyvall, H.G.,Dunlop, J.L.,Jamieson, S.A.,Curry, J.R.,Burke, J.E.,Filipcik, P.,Brown, S.H.J.,Mace, P.D. DET1 dynamics underlie cooperative ubiquitination by CRL4 DET1-COP1 complexes. Sci Adv, 11:eadq4187-eadq4187, 2025 Cited by PubMed Abstract: Transcription factor ubiquitination is a decisive regulator of growth and development. The DET1-DDB1-DDA1 (DDD) complex associates with the Cullin-4 ubiquitin ligase (CRL4) and a second ubiquitin ligase, COP1, to control ubiquitination of transcription factors involved in neurological, metabolic, and immune cell development. Here, we report the structure of the human DDD complex, revealing a specific segment of DET1 that can recruit ubiquitin-conjugating (E2) enzymes. Structural variability analysis, mass spectrometry, and mutagenesis based on AlphaFold predictions suggest that dynamic closure of DET1, stabilized by DDA1, underlies coordinated recruitment of E2 enzymes and COP1. Biochemical assays suggest that the E2 acts as a recruitment factor to bring COP1 to DET1 for more effective substrate ubiquitination, which parallels a catalytically inactive E2 enzyme (COP10) in plant DDD complexes. This work provides a clear architecture for regulation and cooperative CRL4 complex assembly, which can affect degradation of diverse targets by COP1 complexes. PubMed: 40009677DOI: 10.1126/sciadv.adq4187 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.83 Å) |
Structure validation
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