Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Curr Opin Struct Biol. 2021 Apr;67:101-109. doi: 10.1016/j.sbi.2020.10.007. Epub 2020 Nov 5.
RING E3s comprise the largest family of ubiquitin (UB) and ubiquitin-like protein (UBL) ligases. RING E3s typically promote UB or UBL transfer from the active site of an associated E2 enzyme to a distally-recruited substrate. Many RING E3s - including the cullin-RING ligase family - are multifunctional, interacting with various E2s (or other E3s) to target distinct proteins, transfer different UBLs, or to initially modify substrates with UB or subsequently elongate UB chains. Here we consider recent structures of cullin-RING ligases, and their partner E2 enzymes, representing ligation reactions. The studies collectively reveal multimodal mechanisms - interactions between ancillary E2 or E3 domains, post-translational modifications, or auxiliary binding partners - directing cullin-RING E3-E2 enzyme active sites to modify their specific targets.
RING E3s 包含最大的泛素 (UB) 和泛素样蛋白 (UBL) 连接酶家族。RING E3s 通常促进与相关 E2 酶的活性位点相连的 UB 或 UBL 转移到远端募集的底物上。许多 RING E3s（包括 cullin-RING 连接酶家族）具有多功能性，与各种 E2s（或其他 E3s）相互作用，以靶向不同的蛋白质、转移不同的 UBL，或最初用 UB 修饰底物，随后延长 UB 链。在这里，我们考虑 cullin-RING 连接酶及其伴侣 E2 酶的最新结构，这些结构代表连接反应。这些研究共同揭示了多模式机制 - 辅助 E2 或 E3 结构域之间的相互作用、翻译后修饰或辅助结合伙伴 - 指导 cullin-RING E3-E2 酶活性位点修饰其特定的靶标。
