Horn-Ghetko Daniel, Schulman Brenda A
Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, 82152, Germany.
Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, 82152, Germany.
Curr Opin Struct Biol. 2022 Apr;73:102341. doi: 10.1016/j.sbi.2022.102341. Epub 2022 Feb 25.
Specificity in the ubiquitin system depends on E3 ligases, largely belonging to a handful of families discovered more than a decade ago. However, the last two years brought a quantum leap in the identification and/or mechanistic characterization of eukaryotic ubiquitin ligases, in part through implementation of activity-based chemical probes and cryo-EM. Here, we survey recent discoveries of RING-Cys-Relay, RZ-finger, and neddylated cullin-RING-ARIH RBR E3-E3 ubiquitin ligase mechanisms. These ligases transfer ubiquitin through unprecedented mechanisms-via novel catalytic domains or domain combinations-and collectively modify unconventional amino acids, non-proteinaceous bacterial lipid targets, and structurally-diverse substrates recruited to numerous cullin-RING ligases. We anticipate major expansion of the types, features, and mechanisms of E3 ligases will emerge from such chemical and structural approaches in the coming years.
泛素系统的特异性取决于E3连接酶，这些酶大多属于十多年前发现的少数几个家族。然而，在过去两年中，真核泛素连接酶的鉴定和/或机制表征取得了重大飞跃，部分原因是基于活性的化学探针和冷冻电镜的应用。在这里，我们综述了RING-Cys-Relay、RZ-手指和经NEDD化修饰的cullin-RING-ARIH RBR E3-E3泛素连接酶机制的最新发现。这些连接酶通过前所未有的机制——通过新的催化结构域或结构域组合——转移泛素，并共同修饰非常规氨基酸、非蛋白质类细菌脂质靶点以及被招募到众多cullin-RING连接酶的结构多样的底物。我们预计，未来几年，通过此类化学和结构方法，E3连接酶的类型、特征和机制将得到重大扩展。
