+Open data
-Basic information
Entry | Database: PDB / ID: 4a0p | |||||||||
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Title | Crystal structure of LRP6P3E3P4E4 | |||||||||
Components | LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 6 | |||||||||
Keywords | SIGNALING / LRP6 / WNT SIGNALLING / WNT3A / DKK1 / MESD | |||||||||
Function / homology | Function and homology information Wnt-Frizzled-LRP5/6 complex / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / Signaling by RNF43 mutants / neural crest formation / kinase inhibitor activity / toxin transmembrane transporter activity / Wnt receptor activity / low-density lipoprotein particle receptor activity / Wnt-protein binding / cellular response to cholesterol ...Wnt-Frizzled-LRP5/6 complex / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / Signaling by RNF43 mutants / neural crest formation / kinase inhibitor activity / toxin transmembrane transporter activity / Wnt receptor activity / low-density lipoprotein particle receptor activity / Wnt-protein binding / cellular response to cholesterol / midbrain dopaminergic neuron differentiation / negative regulation of protein serine/threonine kinase activity / dopaminergic neuron differentiation / frizzled binding / Wnt signalosome / neural crest cell differentiation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / negative regulation of smooth muscle cell apoptotic process / canonical Wnt signaling pathway / coreceptor activity / positive regulation of cell cycle / Regulation of FZD by ubiquitination / TCF dependent signaling in response to WNT / protein localization to plasma membrane / cell-cell adhesion / positive regulation of DNA-binding transcription factor activity / Wnt signaling pathway / response to peptide hormone / endocytosis / early endosome membrane / nervous system development / positive regulation of cytosolic calcium ion concentration / cytoplasmic vesicle / chemical synaptic transmission / membrane raft / signaling receptor binding / neuronal cell body / synapse / positive regulation of DNA-templated transcription / cell surface / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / extracellular region / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | HOMO SAPIENS (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | |||||||||
Authors | Chen, S. / Malinauskas, T. / Aricescu, A.R. / Siebold, C. / Jones, E.Y. | |||||||||
Citation | Journal: Dev Cell / Year: 2011 Title: Structural and functional studies of LRP6 ectodomain reveal a platform for Wnt signaling. Authors: Shuo Chen / Doryen Bubeck / Bryan T MacDonald / Wen-Xue Liang / Jian-Hua Mao / Tomas Malinauskas / Oscar Llorca / A Radu Aricescu / Christian Siebold / Xi He / E Yvonne Jones / 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) ...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. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4a0p.cif.gz | 279.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4a0p.ent.gz | 225.2 KB | Display | PDB format |
PDBx/mmJSON format | 4a0p.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4a0p_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 4a0p_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 4a0p_validation.xml.gz | 27.3 KB | Display | |
Data in CIF | 4a0p_validation.cif.gz | 40.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/a0/4a0p ftp://data.pdbj.org/pub/pdb/validation_reports/a0/4a0p | HTTPS FTP |
-Related structure data
Related structure data | 1964C 1965C 1ijqS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 71170.094 Da / Num. of mol.: 1 / Fragment: P3E3P4E4, RESIDUES 629-1244 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: C0019 / Cell line (production host): HEK293S / Production host: HOMO SAPIENS (human) / References: UniProt: O75581 |
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-Sugars , 2 types, 4 molecules
#2: Polysaccharide | Source method: isolated from a genetically manipulated source #3: Sugar | |
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-Non-polymers , 4 types, 445 molecules
#4: Chemical | #5: Chemical | #6: Chemical | #7: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.03 Å3/Da / Density % sol: 59.37 % / Description: NONE |
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.9778 |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9778 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→30 Å / Num. obs: 66493 / % possible obs: 98 % / Observed criterion σ(I): 2 / Redundancy: 4.1 % / Rmerge(I) obs: 0.1 / Net I/σ(I): 9.4 |
Reflection shell | Resolution: 1.9→1.95 Å / Redundancy: 3 % / Rmerge(I) obs: 0.56 / Mean I/σ(I) obs: 2 / % possible all: 88.4 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1IJQ Resolution: 1.9→29.09 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.943 / SU B: 4.895 / SU ML: 0.065 / Cross valid method: THROUGHOUT / ESU R: 0.127 / ESU R Free: 0.12 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 23.951 Å2
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Refinement step | Cycle: LAST / Resolution: 1.9→29.09 Å
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