Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP.
Open Biol. 2020 Nov;10(11):200319. doi: 10.1098/rsob.200319. Epub 2020 Nov 25.
The ubiquitin-proteasome system (UPS) is responsible for the rapid targeting of proteins for degradation at 26S proteasomes and requires the orchestrated action of E1, E2 and E3 enzymes in a well-defined cascade. F-box proteins (FBPs) are substrate-recruiting subunits of Skp1-cullin1-FBP (SCF)-type E3 ubiquitin ligases that determine which proteins are ubiquitinated. To date, around 70 FBPs have been identified in humans and can be subdivided into distinct families, based on the protein-recruiting domains they possess. The FBXL subfamily is defined by the presence of multiple leucine-rich repeat (LRR) protein-binding domains. But how the 22 FBPs of the FBXL family achieve their individual specificities, despite having highly similar structural domains to recruit their substrates, is not clear. Here, we review and explore the FBXL family members in detail highlighting their structural and functional similarities and differences and how they engage their substrates through their LRRs to adopt unique interactomes.
泛素-蛋白酶体系统 (UPS) 负责将蛋白质快速靶向到 26S 蛋白酶体进行降解，这需要 E1、E2 和 E3 酶在明确的级联反应中协调作用。F -box 蛋白 (FBPs) 是 Skp1-cullin1-FBP (SCF)-型 E3 泛素连接酶的底物募集亚基，决定哪些蛋白质被泛素化。迄今为止，在人类中已鉴定出约 70 种 FBP，可根据它们所具有的蛋白募集结构域分为不同的家族。FBXL 亚家族的特征是存在多个富含亮氨酸重复 (LRR) 蛋白结合结构域。但是，尽管 FBXL 家族的 22 种 FBP 具有高度相似的结构域来募集其底物，但它们如何实现各自的特异性尚不清楚。在这里，我们详细回顾和探讨了 FBXL 家族成员，强调了它们的结构和功能相似性和差异性，以及它们如何通过 LRR 与底物结合，从而形成独特的相互作用组。
