6l6r

Crystal structure of LRP6 E1E2-SOST complex

spinqualitylabelsall models 6l6r, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6l6r is a 4 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 3.8Å Ligands: ACT, FUC, MG, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease LRP6_HUMAN Coronary artery disease - hyperlipidemia - hypertension - diabetes - osteoporosis. The disease is caused by mutations affecting the gene represented in this entry. Function LRP6_HUMAN Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity). Publication Abstract from PubMed Low-density lipoprotein receptor-related protein 6 (LRP6) is a coreceptor of the beta-catenin-dependent Wnt signaling pathway. The LRP6 ectodomain binds Wnt proteins, as well as Wnt inhibitors such as sclerostin (SOST), which negatively regulates Wnt signaling in osteocytes. Although LRP6 ectodomain 1 (E1) is known to interact with SOST, several unresolved questions remain, such as the reason why SOST binds to LRP6 E1E2 with higher affinity than to the E1 domain alone. Here, we present the crystal structure of the LRP6 E1E2-SOST complex with two interaction sites in tandem. The unexpected additional binding site was identified between the C-terminus of SOST and the LRP6 E2 domain. This interaction was confirmed by in vitro binding and cell-based signaling assays. Its functional significance was further demonstrated in vivo using Xenopus laevis embryos. Our results provide insights into the inhibitory mechanism of SOST on Wnt signaling. Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains.,Kim J, Han W, Park T, Kim EJ, Bang I, Lee HS, Jeong Y, Roh K, Kim J, Kim JS, Kang C, Seok C, Han JK, Choi HJ Nat Commun. 2020 Oct 23;11(1):5357. doi: 10.1038/s41467-020-19155-4. PMID:33097721 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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