5k19

Crystal structure of WD repeat-containing protein 20

spinqualitylabelsall models 5k19, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5k19 is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, SO4 Related: 5k1c, 5k1a, 5k1b, 5k16 Gene: WDR20 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms. Here we report on a series of crystallographic and biochemical analyses of an evolutionarily conserved deubiquitinase, USP12, which is activated by two beta-propeller proteins, UAF1 and WDR20. Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center. Without increasing the substrate affinity of USP12, the two beta-propeller proteins potentiate the enzyme through different allosteric mechanisms. UAF1 docks at the distal end of the USP12 Fingers domain and induces a cascade of structural changes that reach a critical ubiquitin-contacting loop adjacent to the catalytic cleft. By contrast, WDR20 anchors at the base of this loop and remotely modulates the catalytic center of the enzyme. Our results provide a mechanistic example for allosteric activation of USPs by their regulatory partners. Allosteric Activation of Ubiquitin-Specific Proteases by beta-Propeller Proteins UAF1 and WDR20.,Li H, Lim KS, Kim H, Hinds TR, Jo U, Mao H, Weller CE, Sun J, Chatterjee C, D'Andrea AD, Zheng N Mol Cell. 2016 Jul 21;63(2):249-60. doi: 10.1016/j.molcel.2016.05.031. Epub 2016 , Jun 30. PMID:27373336 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also WD repeat-containing protein

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