Transcriptome sequencing data of lge1-D287K and bre1-K528E
The mono-ubiquitination of the histone protein H2B (H2BUb1) has important functions in transcription, DNA repair and many other processes. The reaction is catalyzed by Bre1 and the RNF20-RNF40 complex in the budding yeast and human cells, respectively, and is promoted by Lge1 and WAC that bind to them. The structural basis of these interaction is poorly understood. Here we present crystal structure of the Bre1-Lge1 complex and an AlphaFold predicted structure of the RNF20-RNF40 complex bound with WAC. The structures revealed extensive interfaces between Bre1 and Lge1 and between the RNF20-RNF40 complex and WAC, and structural homology between these interfaces. Structure guided interaction studies revealed entirely different sets of key electrostatic interactions at these interfaces that are crucial for the binding and encode the binding specificity. Further functional studies revealed that these interactions are crucial for the Bre1-catalyzed H2BUb1 reaction and its function inside the cell. Our study provides insights into the Bre1-Lge1 interaction and the related interaction between the RNF20-RNF40 complex and WAC.