CUL1-RBX1-SKP1-FBXO4 SCF 泛素连接酶复合物的结构。

Structure of the CUL1-RBX1-SKP1-FBXO4 SCF ubiquitin ligase complex.

机构信息

MOE Key Laboratory for Membraneless Organelles & Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, 230027, Hefei, PR China.

出版信息

Biochem Biophys Res Commun. 2024 Nov 26;735:150811. doi: 10.1016/j.bbrc.2024.150811. Epub 2024 Oct 11.

DOI:10.1016/j.bbrc.2024.150811

PMID:39406020

Abstract

Cullin-RING E3 ubiquitin ligases (CRLs) constitute the largest family of ubiquitin ligase and play important roles in regulation of proteostasis. Here we presented the cryo-EM structure of CRL1, a member of Cullin-1 E3 ligase. CRL1 adopts a homodimer architecture. Structural analysis revealed that in the CRL1 protomer, the substrate recognition subunit FBXO4 interacts both the adaptor protein SKP1, and the scaffold protein CUL1 via hydrophobic and electrostatic interactions. Two FBXO4 forms a domain-swapped dimer in the CRL1 structure, which constitutes the basis for the dimerization of CRL1. Inspired by the cryo-EM density, we modeled the architecture of whole CRL1 as a symmetrical dimer, which provides insights into CRL1-medaited turnover of oncogene proteins.

摘要

Cullin-RING E3 泛素连接酶（CRLs）构成了最大的泛素连接酶家族，在蛋白质稳态的调节中发挥着重要作用。在这里，我们展示了 Cullin-1 E3 连接酶的一个成员 CRL1 的冷冻电镜结构。CRL1 采用同源二聚体结构。结构分析表明，在 CRL1 原聚体中，底物识别亚基 FBXO4 通过疏水相互作用和静电相互作用与衔接蛋白 SKP1 和支架蛋白 CUL1 相互作用。两个 FBXO4 在 CRL1 结构中形成一个结构域交换二聚体，这构成了 CRL1 二聚化的基础。受冷冻电镜密度的启发，我们将整个 CRL1 的结构建模为对称二聚体，这为 CRL1 介导的致癌蛋白周转提供了深入的了解。