9SO9
BRCA1-A complex bound to K63-oligoUbATA - closed form StateC*
This is a non-PDB format compatible entry.
Summary for 9SO9
| Entry DOI | 10.2210/pdb9so9/pdb |
| Related | 9SMN 9SMP 9SMR 9SMS 9SNA |
| EMDB information | 55053 |
| Descriptor | BRCA1-A complex subunit Abraxas 1, Lys-63-specific deubiquitinase BRCC36, BRISC and BRCA1-A complex member 2, ... (9 entities in total) |
| Functional Keywords | deubiquitinase; dna repair; metalloprotein; ubiquitin chains;, metal binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 13 |
| Total formula weight | 394691.75 |
| Authors | Murachelli, A.G.,Sixma, T.K. (deposition date: 2025-09-12, release date: 2026-06-17, Last modification date: 2026-08-19) |
| Primary citation | Murachelli, A.G.,El Oualid, F.,Sixma, T.K. A ubiquitin chain-feeding mechanism for BRCA1-A. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: The BRCA1-A complex is a multi-subunit, metallo-deubiquitinating enzyme (metallo-DUB) involved in genome maintenance. BRCA1-A displays strict specificity for K63-linked ubiquitin, with a strong preference for long chains, but the mechanistic basis for this selectivity has remained unclear. To address this, we have developed an activity-based probe that is specific for metallo-DUBs and mimics di- or polyubiquitin chains of any linkage (di- and poly-ubiquitin). We have solved cryoEM structures of BRCA1-A bound to K63-linked probe chains of various length, capturing multiple conformational and catalytic states. The structures reveal how allosteric regulation of catalysis occurs within the complex and how BRCA1-A uses auxiliary ubiquitin-binding sites to engage substrate by avidity and to trigger processive cleavage. Crucially, avidity and processivity can only apply to long polyubiquitin chains, explaining BRCA1-A's substrate preference. Together, these results establish BRCA1-A as a chain-shortening DUB specialised for trimming extended K63-linked polyubiquitin chains. PubMed: 42581048DOI: 10.1038/s41467-026-75797-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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