Department of Chemistry and Biochemistry University of California San Diego MC 0309, 1200B Tata Hall 9325 S Scholars Dr, San Diego, CA 92161, USA.
Department of Chemistry and Biochemistry University of California San Diego MC 0309, 1200B Tata Hall 9325 S Scholars Dr, San Diego, CA 92161, USA.
Curr Opin Struct Biol. 2024 Oct;88:102879. doi: 10.1016/j.sbi.2024.102879. Epub 2024 Jul 15.
The cellular process by which the protein ubiquitin (Ub) is covalently attached to a protein substrate involves Ub activating (E1s) and conjugating enzymes (E2s) that work together with a large variety of E3 ligases that impart substrate specificity. The largest family of E3s is the Cullin-RING ligase (CRL) family which utilizes a wide variety of substrate receptors, adapter proteins, and cooperating ligases. Cryo-electron microscopy (cryoEM) has revealed a wide variety of structures which suggest how Ub transfer occurs. Hydrogen deuterium exchange mass spectrometry (HDXMS) has revealed the role of dynamics and expanded our knowledge of how covalent NEDD8 modification (neddylation) activates the CRLs, particularly by facilitating cooperation with additional RING-between-RING ligases to transfer Ub.
蛋白质泛素 (Ub) 与蛋白质底物发生共价连接的细胞过程涉及 Ub 激活酶 (E1s) 和连接酶 (E2s)，它们与多种 E3 连接酶一起作用，赋予底物特异性。E3 连接酶最大的家族是 Cullin-RING 连接酶 (CRL) 家族，它利用各种底物受体、衔接蛋白和协同连接酶。低温电子显微镜 (cryoEM) 揭示了多种结构，这些结构表明 Ub 转移是如何发生的。氢氘交换质谱 (HDXMS) 揭示了动态的作用，并扩展了我们对共价 NEDD8 修饰 (neddylation) 如何激活 CRL 的认识，特别是通过促进与额外的 RING 之间的 RING 连接酶的合作来转移 Ub。
