| Autor: |
Ai, Huasong, Tong, Zebin, Deng, Zhiheng, Shi, Qiang, Tao, Shixian, Sun, Gaoge, Liang, Jiawei, Sun, Maoshen, Wu, Xiangwei, Zheng, Qingyun, Liang, Lujun, Yin, Hang, Li, Jia-Bin, Gao, Shuai, Tian, Changlin, Liu, Lei, Pan, Man |
| Zdroj: |
Nature Chemical Biology; 20240101, Issue: Preprints p1-13, 13p |
| Abstrakt: |
The DNA damage repair regulatory protein RNF168, a monomeric RING-type E3 ligase, has a crucial role in regulating cell fate and DNA repair by specific and efficient ubiquitination of the adjacent K13 and K15 (K13/15) sites at the H2A N-terminal tail. However, understanding how RNF168 coordinates with its cognate E2 enzyme UbcH5c to site-specifically ubiquitinate H2A K13/15 has long been hampered by the lack of high-resolution structures of RNF168 and UbcH5c~Ub (ubiquitin) in complex with nucleosomes. Here we developed chemical strategies and determined the cryo-electron microscopy structures of the RNF168–UbcH5c~Ub–nucleosome complex captured in transient H2A K13/15 monoubiquitination and adjacent dual monoubiquitination reactions, providing a ‘helix-anchoring’ mode for monomeric E3 ligase RNF168 on nucleosome in contrast to the ‘compass-binding’ mode of dimeric E3 ligases. Our work not only provides structural snapshots of H2A K13/15 site-specific monoubiquitination and adjacent dual monoubiquitination but also offers a near-atomic-resolution structural framework for understanding pathogenic amino acid substitutions and physiological modifications of RNF168. |
| Databáze: |
Supplemental Index |
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