9M3I

Crystal structure of the Bre1-Lge1 complex

Summary for 9M3I

• Entry DOI: 10.2210/pdb9m3i/pdb
• Descriptor: E3 ubiquitin-protein ligase BRE1, Transcriptional regulatory protein LGE1 (3 entities in total)
• Functional Keywords: ubiquitin ligase, gene regulation
• Biological source: Saccharomyces cerevisiae S288C; More
• Total number of polymer chains: 5
• Total formula weight: 117601.05

Authors

Zhang, H.,Xiang, S. (deposition date: 2025-03-02, release date: 2026-01-14, Last modification date: 2026-03-04)

Primary citation

Shi, M.,Wang, X.,Zhang, H.,Wen, Y.,Liu, Q.,Chen, P.,Chen, X.,Xiang, S.
Structural insights into the Bre1-Lge1 and RNF20/RNF40-WAC interactions critical for H2B ubiquitination.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: The mono-ubiquitination of the histone protein H2B (H2BUb1) has important functions in transcription, DNA repair, and other chromatin-related processes. The reaction is catalyzed by Bre1 and the homologous RNF20/RNF40 complex in the budding yeast and human cells, respectively, and is promoted by their respective interaction partners, Lge1 and WAC. The mechanism of the Bre1-Lge1 and RNF20/RNF40-WAC interactions is poorly understood. Here, we present the crystal structure of the Bre1-Lge1 complex and an AlphaFold predicted structure model of the RNF20/RNF40 complex bound with WAC, as well as in vitro and in vivo experiments to assess the interaction mechanism and function. Our study revealed extensive Bre1-Lge1 and RNF20/RNF40-WAC interfaces and a structural homology shared by these interfaces, but completely different sets of key electrostatic interactions at these interfaces that are crucial for the binding and encode the binding specificity. We further found that these interactions play critical roles in the Bre1-catalyzed H2BUb1 reaction and processes it regulates. Our data provide insights into the mechanism of the Bre1-Lge1 and RNF20/RNF40-WAC interactions.

PubMed: 41533567
DOI: 10.1093/nar/gkaf1514

Experimental method

X-RAY DIFFRACTION (3.5 Å)