Structural Insight Into the SKP1-CUL1-FBXO3-RBX1 Complex.

IF 2.8 4区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Proteins-Structure Function and Bioinformatics Pub Date : 2025-07-01 Epub Date: 2025-02-08 DOI:10.1002/prot.26809

Jiajia Wei, Chao Xu

引用次数: 0

Abstract

The cryo-EM structure of human SCF^FBXO3, which consists of CUL1, RBX1, SKP1 and FBXO3 was solved at a nominal resolution of 3.70 Å. Although a previous study reported the crystal structure of the FBXO3 ApaG domain, how FBXO3 is incorporated into the SCF complex remains elusive. In the cryo-EM structure of SCF^FBXO3, the F-box domain of FBXO3 primarily associates with SKP1 via extensive hydrophobic interactions and interacts with the N-terminal region of CUL1 via hydrophobic interactions. The weak cryo-EM map of the RBX1 globular region is close to the FBXO3 ApaG domain, suggesting that unmodified SCF^FBXO3 exhibits a closed conformation and that CUL1 neddylation is likely required to achieve high E3 activity. The structural study provides insight into the assembly of SCF^FBXO3 and its activation mediated by CUL1 neddylation.

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SKP1-CUL1-FBXO3-RBX1复合物的结构分析。

由CUL1， RBX1， SKP1和FBXO3组成的人SCFFBXO3的冷冻电镜结构以名义分辨率3.70 Å求解。尽管先前的研究报道了FBXO3 ApaG结构域的晶体结构，但FBXO3如何被纳入SCF复合物仍然是难以捉摸的。在SCFFBXO3的低温电镜结构中，FBXO3的F-box结构域主要通过广泛的疏水相互作用与SKP1结合，并通过疏水相互作用与CUL1的n端区域相互作用。RBX1球形区域的弱低温电镜图接近FBXO3 ApaG结构域，这表明未修饰的SCFFBXO3具有封闭的构象，并且可能需要CUL1类化修饰才能获得高E3活性。该结构研究揭示了SCFFBXO3的组装及其由CUL1类泛素化介导的激活。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Proteins-Structure Function and Bioinformatics 生物-生化与分子生物学

CiteScore

5.90

自引率

3.40%

发文量

172

审稿时长

3 months

期刊介绍： PROTEINS : Structure, Function, and Bioinformatics publishes original reports of significant experimental and analytic research in all areas of protein research: structure, function, computation, genetics, and design. The journal encourages reports that present new experimental or computational approaches for interpreting and understanding data from biophysical chemistry, structural studies of proteins and macromolecular assemblies, alterations of protein structure and function engineered through techniques of molecular biology and genetics, functional analyses under physiologic conditions, as well as the interactions of proteins with receptors, nucleic acids, or other specific ligands or substrates. Research in protein and peptide biochemistry directed toward synthesizing or characterizing molecules that simulate aspects of the activity of proteins, or that act as inhibitors of protein function, is also within the scope of PROTEINS. In addition to full-length reports, short communications (usually not more than 4 printed pages) and prediction reports are welcome. Reviews are typically by invitation; authors are encouraged to submit proposed topics for consideration.