title: The structural basis of DKK-mediated inhibition of Wnt/LRP signaling.
abstract: Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) mediate canonical Wnt-β-catenin signaling by forming a complex with the co-receptor Frizzled, which binds to Wnt proteins. Dickkopf (DKK)-related proteins inhibit the Wnt signaling pathway by directly binding to the ectodomains of LRP5/6. However, the mechanism for DKK-mediated antagonism has not been fully understood as of yet. Crystal structures of the LRP6 ectodomain in complex with DKK1, along with mutagenesis studies, provide considerable insights into the molecular basis for DKK-mediated inhibition and Wnt signaling through LRP5/6.
authors.affiliation: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Bao
authors.forename: Jie J
authors.initials: JJ
authors.lastname: Zheng
authors.forename: Dianqing
authors.initials: D
authors.lastname: Wu
mesh_terms: D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000502:physiology*; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000378:metabolism*; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C555482:LRP5 protein, human; C555475:LRP6 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051153:Wnt Proteins