Nguyen Henry C, Wang Wei, Xiong Yong
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, CA, 94158, USA.
Subcell Biochem. 2017;83:323-347. doi: 10.1007/978-3-319-46503-6_12.
Ubiquitination is a highly conserved post-translational modification in eukaryotes, well known for targeting proteins for degradation by the 26S proteasome. Proteins destined for proteasomal degradation are selected by E3 ubiquitin ligases. Cullin-RING E3 ubiquitin ligases (CRLs) are the largest superfamily of E3 ubiquitin ligases, with over 400 members known in mammals. These modular complexes are tightly regulated in the cell. In this chapter, we highlight recent structural and biochemical advances shedding light on the assembly and architecture of cullin-RING ligases, their dynamic regulation by a variety of host factors, and their manipulation by viral pathogens and small molecules.
泛素化是真核生物中一种高度保守的翻译后修饰,以靶向蛋白质通过26S蛋白酶体进行降解而闻名。注定要被蛋白酶体降解的蛋白质由E3泛素连接酶选择。Cullin-RING E3泛素连接酶(CRLs)是E3泛素连接酶中最大的超家族,在哺乳动物中有超过400个已知成员。这些模块化复合物在细胞中受到严格调控。在本章中,我们重点介绍了最近在结构和生化方面的进展,这些进展揭示了cullin-RING连接酶的组装和结构、它们受到多种宿主因子的动态调控以及它们被病毒病原体和小分子操纵的情况。