5VZT
Crystal structure of the Skp1-FBXO31 complex
Summary for 5VZT
| Entry DOI | 10.2210/pdb5vzt/pdb |
| Descriptor | S-phase kinase-associated protein 1, F-box only protein 31, ZINC ION, ... (6 entities in total) |
| Functional Keywords | ubiquitin ligase, cell cycle |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 146313.57 |
| Authors | |
| Primary citation | Li, Y.,Jin, K.,Bunker, E.,Zhang, X.,Luo, X.,Liu, X.,Hao, B. Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCFFBXO31 ubiquitin ligase. Proc. Natl. Acad. Sci. U.S.A., 115:319-324, 2018 Cited by PubMed Abstract: Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCF (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. Previous studies have suggested that cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm. Here we present the crystal structures of the Skp1-FBXO31 complex alone and bound to a phosphorylated cyclin D1 C-terminal peptide. FBXO31 possesses a unique substrate-binding domain consisting of two β-barrel motifs, whereas cyclin D1 binds to FBXO31 by tucking its free C-terminal carboxylate tail into an open cavity of the C-terminal FBXO31 β-barrel. Biophysical and functional studies demonstrate that SCF is capable of recruiting and ubiquitinating cyclin D1 in a phosphorylation-independent manner. Our findings provide a conceptual framework for understanding the substrate specificity of the F-box protein FBXO31 and the mechanism of FBXO31-regulated cyclin D1 protein turnover. PubMed: 29279382DOI: 10.1073/pnas.1708677115 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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