5vzu

Crystal structure of the Skp1-FBXO31-cyclin D1 complex

spinqualitylabelsall models 5vzu, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5vzu is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: PO4, TPO, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SKP1_HUMAN Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110. Publication Abstract from PubMed Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCF(FBXO31) (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 beta-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 beta-barrel. Biophysical and functional studies demonstrate that SCF(FBXO31) 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. Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCF(FBXO31) ubiquitin ligase.,Li Y, Jin K, Bunker E, Zhang X, Luo X, Liu X, Hao B Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):319-324. doi:, 10.1073/pnas.1708677115. Epub 2017 Dec 26. PMID:29279382 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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