5YUF

Crystal Structure of PML RING tetramer

5YUF の概要

• エントリーDOI: 10.2210/pdb5yuf/pdb
• 分子名称: Protein PML, ZINC ION (3 entities in total)
• 機能のキーワード: pml nuclear body biogenesis, sumoylation, ring tetramerization, pml-rara, targeted therapy, oncoprotein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: P29590
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 22985.64

構造登録者

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. (登録日: 2017-11-22, 公開日: 2018-04-11, 最終更新日: 2024-11-06)

主引用文献

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

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: 29599493
DOI: 10.1038/s41467-018-03498-0

実験手法

X-RAY DIFFRACTION (1.6 Å)