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| Title | Structure of CRL7 reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation. |
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| Journal, issue, pages | Nat Struct Mol Biol, Vol. 29, Issue 9, Page 854-862, Year 2022 |
| Publish date | Aug 18, 2022 |
 Authors | Linus V M Hopf / Kheewoong Baek / Maren Klügel / Susanne von Gronau / Yue Xiong / Brenda A Schulman /   |
| PubMed Abstract | Most cullin-RING ubiquitin ligases (CRLs) form homologous assemblies between a neddylated cullin-RING catalytic module and a variable substrate-binding receptor (for example, an F-box protein). ...Most cullin-RING ubiquitin ligases (CRLs) form homologous assemblies between a neddylated cullin-RING catalytic module and a variable substrate-binding receptor (for example, an F-box protein). However, the vertebrate-specific CRL7 is of interest because it eludes existing models, yet its constituent cullin CUL7 and F-box protein FBXW8 are essential for development, and CUL7 mutations cause 3M syndrome. In this study, cryo-EM and biochemical analyses reveal the CRL7 assembly. CUL7's exclusivity for FBXW8 among all F-box proteins is explained by its unique F-box-independent binding mode. In CRL7, the RBX1 (also known as ROC1) RING domain is constrained in an orientation incompatible with binding E2~NEDD8 or E2~ubiquitin intermediates. Accordingly, purified recombinant CRL7 lacks auto-neddylation and ubiquitination activities. Instead, our data indicate that CRL7 serves as a substrate receptor linked via SKP1-FBXW8 to a neddylated CUL1-RBX1 catalytic module mediating ubiquitination. The structure reveals a distinctive CRL-CRL partnership, and provides a framework for understanding CUL7 assemblies safeguarding human health. |
 External links | Nat Struct Mol Biol / PubMed:35982156 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.8 - 5.4 Å |
| Structure data | EMDB-14547, PDB-7z8b:  EMDB-14558: Structure of the CUL7-RBX1-FBXW8-SKP1-CUL1 N-terminal region forming multi cullin-RING ligase complex |
| Chemicals |  ChemComp-ZN: |
| Source |
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 Keywords |  LIGASE / Cullin-RING Ubiquitin E3 Ligase |
