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- PDB-8ffe: Crystal structure of LRP6 E1E2 domains bound to YW210.09 Fab and ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8ffe | ||||||
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Title | Crystal structure of LRP6 E1E2 domains bound to YW210.09 Fab and engineered XWnt8 peptide | ||||||
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![]() | SIGNALING PROTEIN/Immune System / WNT / RECEPTOR / LRP5 / LRP6 / LDL RECEPTOR-LIKE PROTEIN / YWTD B-PROPELLER / SIGNALING PROTEIN / SIGNALING PROTEIN-Immune System complex | ||||||
Function / homology | ![]() 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 / Wnt signaling pathway / response to peptide hormone / cell-cell adhesion / positive regulation of DNA-binding transcription factor activity / endocytosis / nervous system development / positive regulation of cytosolic calcium ion concentration / early endosome membrane / cytoplasmic vesicle / chemical synaptic transmission / membrane raft / signaling receptor binding / neuronal cell body / synapse / positive regulation of DNA-templated transcription / cell surface / endoplasmic reticulum / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular region / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Jude, K.M. / Tsutsumi, N. / Waghray, D. / Garcia, K.C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for coreceptor discrimination. Authors: Naotaka Tsutsumi / Sunhee Hwang / Deepa Waghray / Simon Hansen / Kevin M Jude / Nan Wang / Yi Miao / Caleb R Glassman / Nathanael A Caveney / Claudia Y Janda / Rami N Hannoush / K Christopher Garcia / ![]() ![]() ![]() Abstract: Wnt morphogens are critical for embryonic development and tissue regeneration. Canonical Wnts form ternary receptor complexes composed of tissue-specific Frizzled (Fzd) receptors together with the ...Wnt morphogens are critical for embryonic development and tissue regeneration. Canonical Wnts form ternary receptor complexes composed of tissue-specific Frizzled (Fzd) receptors together with the shared LRP5/6 coreceptors to initiate β-catenin signaling. The cryo-EM structure of a ternary initiation complex of an affinity-matured XWnt8-Frizzled8-LRP6 complex elucidates the basis of coreceptor discrimination by canonical Wnts by means of their N termini and linker domains that engage the LRP6 E1E2 domain funnels. Chimeric Wnts bearing modular linker "grafts" were able to transfer LRP6 domain specificity between different Wnts and enable non-canonical Wnt5a to signal through the canonical pathway. Synthetic peptides comprising the linker domain serve as Wnt-specific antagonists. The structure of the ternary complex provides a topological blueprint for the orientation and proximity of Frizzled and LRP6 within the Wnt cell surface signalosome. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 534 KB | Display | ![]() |
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PDB format | ![]() | 362.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 8ctgC C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
Experimental dataset #1 | Data reference: ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 69302.148 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Antibody , 2 types, 2 molecules HL
#2: Antibody | Mass: 28657.805 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: engineered Wnt8 peptide (position 1-18) is originally from Xenopus laevis Source: (gene. exp.) ![]() ![]() |
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#3: Antibody | Mass: 24426.025 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 3 types, 3 molecules
#4: Polysaccharide | alpha-L-fucopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)][alpha-L-fucopyranose-(1- ...alpha-L-fucopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#5: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#6: Polysaccharide | alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]2-acetamido-2-deoxy- ...alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source |
-Non-polymers , 4 types, 603 molecules ![](data/chem/img/GOL.gif)
![](data/chem/img/NA.gif)
![](data/chem/img/SIN.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/NA.gif)
![](data/chem/img/SIN.gif)
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#7: Chemical | ChemComp-GOL / #8: Chemical | #9: Chemical | ChemComp-SIN / | #10: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.36 Å3/Da / Density % sol: 47.95 % / Description: rectangluar prism |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 Details: 100 mM SPG (succinate/phosphate/glycine buffer), 25% PEG 1500 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 14, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 |
Reflection | Resolution: 1.72→44.37 Å / Num. obs: 109415 / % possible obs: 90.56 % / Redundancy: 7.1 % / Biso Wilson estimate: 30.74 Å2 / CC1/2: 0.997 / CC star: 0.999 / Rpim(I) all: 0.03889 / Rrim(I) all: 0.1042 / Rsym value: 0.09658 / Net I/σ(I): 10.49 |
Reflection shell | Resolution: 1.72→1.781 Å / Redundancy: 6.7 % / Mean I/σ(I) obs: 0.64 / Num. unique obs: 6719 / CC1/2: 0.426 / CC star: 0.773 / Rpim(I) all: 0.8556 / Rrim(I) all: 2.243 / Rsym value: 2.068 / % possible all: 55.47 |
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Processing
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Refinement | Method to determine structure: ![]() Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 38.7 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.72→44.37 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group | Refine-ID: X-RAY DIFFRACTION
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