8UQE
Crystal structure of RNF168 (RING)-UbcH5c fused to H2A-H2B via a 26-residue linker (RING not modeled in density)
Summary for 8UQE
| Entry DOI | 10.2210/pdb8uqe/pdb |
| Descriptor | E3 ubiquitin-protein ligase RNF168,Ubiquitin-conjugating enzyme E2 D3,Histone H2B type 2-E,Histone H2A type 1-B/E (1 entity in total) |
| Functional Keywords | rnf168, ubch5c, histone h2a, histone h2b, chromatin, ubiquitin ligase, ubiquitin-conjugating enzyme, dna damage response, dna double-strand break repair, protein binding, protein binding-transferase complex, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 50542.83 |
| Authors | Hu, Q.,Botuyan, M.V.,Mer, G. (deposition date: 2023-10-23, release date: 2024-01-17, Last modification date: 2024-03-20) |
| Primary citation | Hu, Q.,Zhao, D.,Cui, G.,Bhandari, J.,Thompson, J.R.,Botuyan, M.V.,Mer, G. Mechanisms of RNF168 nucleosome recognition and ubiquitylation. Mol.Cell, 84:839-853.e12, 2024 Cited by PubMed Abstract: RNF168 plays a central role in the DNA damage response (DDR) by ubiquitylating histone H2A at K13 and K15. These modifications direct BRCA1-BARD1 and 53BP1 foci formation in chromatin, essential for cell-cycle-dependent DNA double-strand break (DSB) repair pathway selection. The mechanism by which RNF168 catalyzes the targeted accumulation of H2A ubiquitin conjugates to form repair foci around DSBs remains unclear. Here, using cryoelectron microscopy (cryo-EM), nuclear magnetic resonance (NMR) spectroscopy, and functional assays, we provide a molecular description of the reaction cycle and dynamics of RNF168 as it modifies the nucleosome and recognizes its ubiquitylation products. We demonstrate an interaction of a canonical ubiquitin-binding domain within full-length RNF168, which not only engages ubiquitin but also the nucleosome surface, clarifying how such site-specific ubiquitin recognition propels a signal amplification loop. Beyond offering mechanistic insights into a key DDR protein, our study aids in understanding site specificity in both generating and interpreting chromatin ubiquitylation. PubMed: 38242129DOI: 10.1016/j.molcel.2023.12.036 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.562 Å) |
Structure validation
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