4A0P
Crystal structure of LRP6P3E3P4E4
Summary for 4A0P
| Entry DOI | 10.2210/pdb4a0p/pdb |
| Descriptor | LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 6, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | signaling, lrp6, wnt signalling, wnt3a, dkk1, mesd |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 72812.04 |
| Authors | Chen, S.,Malinauskas, T.,Aricescu, A.R.,Siebold, C.,Jones, E.Y. (deposition date: 2011-09-11, release date: 2011-10-26, Last modification date: 2024-11-06) |
| Primary citation | Chen, S.,Bubeck, D.,Macdonald, B.T.,Liang, W.X.,Mao, J.H.,Malinauskas, T.,Llorca, O.,Aricescu, A.R.,Siebold, C.,He, X.,Jones, E.Y. Structural and Functional Studies of Lrp6 Ectodomain Reveal a Platform for Wnt Signaling. Dev.Cell, 21:848-, 2011 Cited by PubMed Abstract: LDL-receptor-related protein 6 (LRP6), alongside Frizzled receptors, transduces Wnt signaling across the plasma membrane. The LRP6 ectodomain comprises four tandem β-propeller-EGF-like domain (PE) pairs that harbor binding sites for Wnt morphogens and their antagonists including Dickkopf 1 (Dkk1). To understand how these multiple interactions are integrated, we combined crystallographic analysis of the third and fourth PE pairs with electron microscopy (EM) to determine the complete ectodomain structure. An extensive inter-pair interface, conserved for the first-to-second and third-to-fourth PE interactions, contributes to a compact platform-like architecture, which is disrupted by mutations implicated in developmental diseases. EM reconstruction of the LRP6 platform bound to chaperone Mesd exemplifies a binding mode spanning PE pairs. Cellular and binding assays identify overlapping Wnt3a- and Dkk1-binding surfaces on the third PE pair, consistent with steric competition, but also suggest a model in which the platform structure supports an interplay of ligands through multiple interaction sites. PubMed: 22000855DOI: 10.1016/J.DEVCEL.2011.09.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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