8IEG

Bre1(mRBD-RING)/Rad6-Ub/nucleosome complex

Summary for 8IEG

• Entry DOI: 10.2210/pdb8ieg/pdb
• EMDB information: 35381
• Descriptor: Histone H3.1, ZINC ION, Histone H4, ... (10 entities in total)
• Functional Keywords: nucleosome, bre1, rad6, ub, nuclear protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 208876.43

Authors

Ai, H.,Deng, Z.,Pan, M.,Liu, L. (deposition date: 2023-02-15, release date: 2023-09-06, Last modification date: 2023-09-20)

Primary citation

Deng, Z.,Ai, H.,Sun, M.,Tong, Z.,Du, Y.,Qu, Q.,Zhang, L.,Xu, Z.,Tao, S.,Shi, Q.,Li, J.B.,Pan, M.,Liu, L.
Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A.
Mol.Cell, 83:3080-3094.e14, 2023

PubMed Abstract: Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme (yeast Rad6 or human hRAD6A), together, precisely deposit ubiquitin on H2B K123 in yeast or K120 in humans. Here, we developed a chemical trapping strategy and successfully captured the transient structures of Bre1- or RNF20/RNF40-mediated ubiquitin transfer from Rad6 or hRAD6A to nucleosomal H2B. Our structures show that Bre1 and RNF40 directly bind nucleosomal DNA, exhibiting a conserved E3/E2/nucleosome interaction pattern from yeast to humans for H2B monoubiquitylation. We also find an uncanonical non-hydrophobic contact in the Bre1 RING-Rad6 interface, which positions Rad6 directly above the target H2B lysine residue. Our study provides mechanistic insights into the site-specific monoubiquitylation of H2B, reveals a critical role of nucleosomal DNA in mediating E3 ligase recognition, and provides a framework for understanding the cancer-driving mutations of RNF20/RNF40.

PubMed: 37633270
DOI: 10.1016/j.molcel.2023.08.001

Experimental method

ELECTRON MICROSCOPY (3.44 Å)