4c8c

mouse ZNRF3 ectodomain crystal form III

spinqualitylabelsall models 4c8c, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4c8c is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 4c84, 4c85, 4c86, 4c8a, 4c8f, 4c8p, 4c8t, 4c8v, 4c8w, 4c99, 4c9a, 4c9e, 4c9r, 4c9u, 4c9v Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ZNRF3_MOUSE] E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone. Publication Abstract from PubMed The four R-spondin (Rspo) proteins are secreted agonists of Wnt signalling in vertebrates, functioning in embryogenesis and adult stem cell biology. Through ubiquitination and degradation of Wnt receptors, the transmembrane E3 ubiquitin ligase ZNRF3 and related RNF43 antagonize Wnt signalling. Rspo ligands have been reported to inhibit the ligase activity through direct interaction with ZNRF3 and RNF43. Here we report multiple crystal structures of the ZNRF3 ectodomain (ZNRF3ecto), a signalling-competent Furin1-Furin2 (Fu1-Fu2) fragment of Rspo2 (Rspo2Fu1-Fu2), and Rspo2Fu1-Fu2 in complex with ZNRF3ecto, or RNF43ecto. A prominent loop in Fu1 clamps into equivalent grooves in the ZNRF3ecto and RNF43ecto surface. Rspo binding enhances dimerization of ZNRF3ecto but not of RNF43ecto. Comparison of the four Rspo proteins, mutants and chimeras in biophysical and cellular assays shows that their signalling potency depends on their ability to recruit ZNRF3 or RNF43 via Fu1 into a complex with LGR receptors, which interact with Rspo via Fu2. Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin.,Zebisch M, Xu Y, Krastev C, Macdonald BT, Chen M, Gilbert RJ, He X, Jones EY Nat Commun. 2013 Nov 14;4:2787. doi: 10.1038/ncomms3787. PMID:24225776 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ubiquitin protein ligase

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