SCF (Skp1-Cullin-F-box) ubiquitin ligases comprise several dozen modular enzymes that have diverse roles in biological regulation. SCF enzymes share a common catalytic core containing Cul1⋅Rbx1, which is directed toward different substrates by a variable substrate receptor (SR) module comprising 1 of 69 F-box proteins bound to Skp1. Despite the broad cellular impact of SCF enzymes, important questions remain about the architecture and regulation of the SCF repertoire, including whether SRs compete for Cul1 and, if so, how this competition is managed. Here, we devise methods that preserve the in vivo assemblages of SCF complexes and apply quantitative mass spectrometry to perform a census of these complexes (the "SCFome") in various states. We show that Nedd8 conjugation and the SR exchange factor Cand1 have a profound effect on shaping the SCFome. Together, these factors enable rapid remodeling of SCF complexes to promote biased assembly of SR modules bound to substrate.

中文翻译：

---

SCF泛素天冬氨酸细胞组成成分的组成和调控。

SCF（Skp1-Cullin-F-box）泛素连接酶包含数十种模块化酶，这些酶在生物调节中具有多种作用。SCF酶共享一个包含Cul1·Rbx1的共同催化核心，该核心通过可变底物受体（SR）模块针对不同的底物，该模块包含与Skp1结合的69个F-box蛋白中的1个。尽管SCF酶对细胞具有广泛的影响，但关于SCF组成部分的结构和调节仍存在重要问题，包括SR是否竞争Cul1，如果竞争，如何管理这种竞争。在这里，我们设计了保留SCF配合物在体内的组合的方法，并应用定量质谱法对这些配合物（“ SCFome”）进行了各种状态的普查。我们表明，Nedd8共轭和SR交换因子Cand1对塑造SCFome具有深远的影响。总之，这些因素使SCF复合物能够快速重塑，从而促进与底物结合的SR模块的偏向组装。