5gje

Three-dimensional reconstruction of human LRP6 ectodomain complexed with Dkk1Three-dimensional reconstruction of human LRP6 ectodomain complexed with Dkk1

5gje, resolution 21.00Å Show:Asymmetric Unit Biological Assembly Structural highlights 5gje is a 3 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: Electron Microscopy, Resolution 21Å Ligands: Experimental data: Check 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 LDL-receptor-related protein 6 (LRP6) is a single-pass membrane glycoprotein with a large modular ectodomain and forms a higher order signaling platform upon binding Wnt ligands on the cell surface. Although multiple crystal structures are available for fragments of the LRP6 ectodomain, we lack a consensus view on the overall molecular architecture of the full-length LRP6 and its dynamic aspects. Here, we used negative-stain electron microscopy to probe conformational states of the entire ectodomain of LRP6 in solution and found that the four-module ectodomain undergoes a large bending motion hinged at the junction between the second and the third modules. Importantly, the extent of inter-domain motion is modulated by evolutionarily conserved N-glycan chains proximal to the joint. We also found that the LRP6 ectodomain becomes highly compact upon complexation with the Wnt antagonist Dkk1, suggesting a potential role for the ectodomain conformational change in the regulation of receptor oligomerization and signaling. Conformational Freedom of the LRP6 Ectodomain Is Regulated by N-glycosylation and the Binding of the Wnt Antagonist Dkk1.,Matoba K, Mihara E, Tamura-Kawakami K, Miyazaki N, Maeda S, Hirai H, Thompson S, Iwasaki K, Takagi J Cell Rep. 2017 Jan 3;18(1):32-40. doi: 10.1016/j.celrep.2016.12.017. PMID:28052259 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.