Building ubiquitination machineries: E3 ligase multi-subunit assembly and substrate targeting by PROTACs and molecular glues
Building ubiquitination machineries: E3 ligase multi-subunit assembly and substrate targeting by PROTACs and molecular glues
复制标题
构建泛素化机制：E3连接酶多亚基组装和通过PROTAC和分子胶的底物靶向
DOI：
10.1016/j.sbi.2020.10.009
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发表时间：
2021-04-01
影响因子：
6.8
通讯作者：
Ciulli, Alessio
中科院分区：
文献类型：
--
作者：
Ramachandran, Sarath;Ciulli, Alessio
E3 ubiquitin ligase machineries are emerging as attractive therapeutic targets because they confer specificity to substrate ubiquitination and can be hijacked for targeted protein degradation. In this review, we bring to focus our current structural understanding of E3 ligase complexes, in particular the multi-subunit cullin RING ligases, and modulation thereof by small-molecule glues and PROTAC degraders. We highlight recent advances in elucidating the modular assembly of E3 ligase machineries, their diverse substrate and degron recognition mechanisms, and how these structural features impact on ligase function. We then outline the emergence of structures of E3 ligases bound to neo-substrates and degrader molecules, and highlight the importance of studying such ternary complexes for structure based degrader design.
