Structural basis for the Rad6 activation by the Bre1 N-terminal domain
- Tianjin Medical University, China
- Wuhan University, China
- Tianjin Medical University General Hospital, China
Abstract
The mono-ubiquitination of the histone protein H2B (H2Bub1) is a highly conserved histone post-translational modification that plays critical roles in many fundamental processes. In yeast, this modification is catalyzed by the conserved Bre1-Rad6 complex. Bre1 contains a unique N-terminal Rad6 binding domain (RBD), how it interacts with Rad6 and contributes to the H2Bub1 catalysis is unclear. Here, we present crystal structure of the Bre1 RBD-Rad6 complex and structure-guided functional studies. Our structure provides a detailed picture of the interaction between the dimeric Bre1 RBD and a single Rad6 molecule. We further found that the interaction stimulates Rad6's enzymatic activity by allosterically increasing its active site accessibility and likely contribute to the H2Bub1 catalysis through additional mechanisms. In line with these important functions, we found that the interaction is crucial for multiple H2Bub1-regulated processes. Our study provides molecular insights into the H2Bub1 catalysis.
Data availability
Diffraction data and refined structures of crystal forms 1 and 2 of the KlBre1 RBD-Rad6 complex have been deposited into the protein data bank (www.rcsb.org), with accession codes 7W75 and 7W76, respectively. All data generated or analysed during this study are included in the manuscript and supporting file; source data files are provided for Figures 1-5, figure 1 figure supplement 3 and figure 3 figure supplement 1.
Article and author information
Author details
Funding
National Natural Science Foundation of China (32271259,32071205 and 31870769)
- Song Xiang
National Natural Science Foundation of China (32070573 and 31872808)
- Xuefeng Chen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Xiaobing Shi, Van Andel Institute, United States
Version history
- Received: October 12, 2022
- Preprint posted: October 24, 2022 (view preprint)
- Accepted: March 10, 2023
- Accepted Manuscript published: March 13, 2023 (version 1)
- Version of Record published: March 23, 2023 (version 2)
Copyright
© 2023, Shi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural basis for the Rad6 activation by the Bre1 N-terminal domain
eLife 12:e84157.
https://doi.org/10.7554/eLife.84157
Further reading
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