5YUF
Crystal Structure of PML RING tetramer
Summary for 5YUF
| Entry DOI | 10.2210/pdb5yuf/pdb |
| Descriptor | Protein PML, ZINC ION (3 entities in total) |
| Functional Keywords | pml nuclear body biogenesis, sumoylation, ring tetramerization, pml-rara, targeted therapy, oncoprotein |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus: P29590 |
| Total number of polymer chains | 4 |
| Total formula weight | 22985.64 |
| Authors | Wang, P.,Benhend, S.,Wu, H.,Breitenbach, V.,Zhen, T.,Jollivet, F.,Peres, L.,Li, Y.,Chen, S.,Chen, Z.,de THE, H.,Meng, G. (deposition date: 2017-11-22, release date: 2018-04-11, Last modification date: 2024-11-06) |
| Primary citation | Wang, P.,Benhenda, S.,Wu, H.,Lallemand-Breitenbach, V.,Zhen, T.,Jollivet, F.,Peres, L.,Li, Y.,Chen, S.J.,Chen, Z.,de The, H.,Meng, G. RING tetramerization is required for nuclear body biogenesis and PML sumoylation. Nat Commun, 9:1277-1277, 2018 Cited by PubMed Abstract: ProMyelocyticLeukemia nuclear bodies (PML NBs) are stress-regulated domains directly implicated in acute promyelocytic leukemia eradication. Most TRIM family members bind ubiquitin E2s and many acquire ligase activity upon RING dimerization. In contrast, PML binds UBC9, the SUMO E2 enzyme. Here, using X-ray crystallography and SAXS characterization, we demonstrate that PML RING tetramerizes through highly conserved PML-specific sequences, which are required for NB assembly and PML sumoylation. Conserved residues implicated in RING dimerization of other TRIMs also contribute to PML tetramer stability. Wild-type PML rescues the ability of some RING mutants to form NBs as well as their sumoylation. Impaired RING tetramerization abolishes PML/RARA-driven leukemogenesis in vivo and arsenic-induced differentiation ex vivo. Our studies thus identify RING tetramerization as a key step in the NB macro-molecular scaffolding. They suggest that higher order RING interactions allow efficient UBC9 recruitment and thus change the biochemical nature of TRIM-facilitated post-translational modifications. PubMed: 29599493DOI: 10.1038/s41467-018-03498-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
Download full validation report
