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) 负责快速靶向蛋白质以在 26S 蛋白酶体处降解，并且需要 E1、E2 和 E3 酶在明确定义的级联中协同作用。F-box 蛋白 (FBP) 是 Skp1-cullin1-FBP (SCF) 型 E3 泛素连接酶的底物募集亚基，可确定哪些蛋白质被泛素化。迄今为止，已经在人类中鉴定了大约 70 个 FBP，并且可以根据它们拥有的蛋白质募集域细分为不同的家族。FBXL 亚家族的定义是存在多个富含亮氨酸的重复 (LRR) 蛋白结合域。但是，尽管 FBXL 家族的 22 个 FBP 具有高度相似的结构域来招募其底物，但它们如何实现各自的特异性尚不清楚。这里，