4bsp

Crystal structure of R-spondin 1 (Fu1Fu2) - Holmium soak

spinqualitylabelsall models 4bsp, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bsp is a 1 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 2Å Ligands: HO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease RSPO1_HUMAN Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma. Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC) [MIM:610644: A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Note=The disease is caused by mutations affecting the gene represented in this entry. Function RSPO1_HUMAN Activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. Acts both in the canonical Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway, probably by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination. Publication Abstract from PubMed Leucine-rich repeat-containing G protein-coupled receptors 4-6 (LGR4-LGR6) are receptors for R-spondins, potent Wnt agonists that exert profound trophic effects on Wnt-driven stem cells compartments. We present crystal structures of a signaling-competent fragment of R-spondin 1 (Rspo1) at a resolution of 2.0 A and its complex with the LGR5 ectodomain at a resolution of 3.2 A. Ecto-LGR5 binds Rspo1 at its concave leucine-rich-repeat (LRR) surface, forming a dimeric 2:2 complex. Fully conserved residues on LGR4-LGR6 explain promiscuous binding of R-spondins. A phenylalanine clamp formed by Rspo1 Phe106 and Phe110 pinches Ala190 of LGR5 and is critical for binding. Mutations related to congenital anonychia reduce signaling, but not binding of Rspo1 to LGR5. Furthermore, antibody binding to the extended loop of the C-terminal LRR cap of LGR5 activates signaling in a ligand-independent manner. Thus, our data reveal binding of R-spondins to conserved sites on LGR4-LGR6 and, in analogy to FSHR and related receptors, suggest a direct signaling role for LGR4-LGR6 in addition to its formation of Wnt receptor and coreceptor complexes. Structure of Stem Cell Growth Factor R-spondin 1 in Complex with the Ectodomain of Its Receptor LGR5.,Peng WC, de Lau W, Forneris F, Granneman JC, Huch M, Clevers H, Gros P Cell Rep. 2013 Jun 27;3(6):1885-92. doi: 10.1016/j.celrep.2013.06.009. PMID:23809763 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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