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- EMDB-9501: Three-dimensional reconstruction of human LRP6 ectodomain complex... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-9501 | |||||||||
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Title | Three-dimensional reconstruction of human LRP6 ectodomain complexed with Dkk1 | |||||||||
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Function / homology | ![]() negative regulation of mesodermal cell fate specification / regulation of endodermal cell fate specification / positive regulation of Wnt signaling pathway, calcium modulating pathway / negative regulation of Wnt-Frizzled-LRP5/6 complex assembly / positive regulation of midbrain dopaminergic neuron differentiation / negative regulation of presynapse assembly / Signaling by LRP5 mutants / Wnt signaling pathway involved in somitogenesis / regulation of dopaminergic neuron differentiation / negative regulation of cardiac muscle cell differentiation ...negative regulation of mesodermal cell fate specification / regulation of endodermal cell fate specification / positive regulation of Wnt signaling pathway, calcium modulating pathway / negative regulation of Wnt-Frizzled-LRP5/6 complex assembly / positive regulation of midbrain dopaminergic neuron differentiation / negative regulation of presynapse assembly / Signaling by LRP5 mutants / Wnt signaling pathway involved in somitogenesis / regulation of dopaminergic neuron differentiation / negative regulation of cardiac muscle cell differentiation / Wnt-Frizzled-LRP5/6 complex / motor learning / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / endoderm formation / synapse pruning / Signaling by RNF43 mutants / neural crest formation / receptor-mediated endocytosis involved in cholesterol transport / endocardial cushion development / regulation of receptor internalization / heart induction / receptor antagonist activity / kinase inhibitor activity / toxin transmembrane transporter activity / low-density lipoprotein particle receptor activity / co-receptor binding / Wnt receptor activity / positive regulation of Wnt signaling pathway, planar cell polarity pathway / cellular response to cholesterol / midbrain dopaminergic neuron differentiation / Wnt-protein binding / negative regulation of protein serine/threonine kinase activity / dopaminergic neuron differentiation / heart valve development / frizzled binding / negative regulation of ossification / Wnt signalosome / neural crest cell differentiation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / embryonic limb morphogenesis / face morphogenesis / limb development / low-density lipoprotein particle receptor binding / negative regulation of SMAD protein signal transduction / negative regulation of Wnt signaling pathway / negative regulation of peptidyl-serine phosphorylation / negative regulation of smooth muscle cell apoptotic process / mesoderm formation / negative regulation of BMP signaling pathway / hair follicle development / canonical Wnt signaling pathway / coreceptor activity / positive regulation of cell cycle / regulation of neuron apoptotic process / response to retinoic acid / forebrain development / regulation of synaptic transmission, glutamatergic / Regulation of FZD by ubiquitination / negative regulation of protein binding / TCF dependent signaling in response to WNT / protein localization to plasma membrane / positive regulation of JNK cascade / growth factor activity / negative regulation of canonical Wnt signaling pathway / cell morphogenesis / Wnt signaling pathway / response to peptide hormone / positive regulation of DNA-binding transcription factor activity / cell-cell adhesion / negative regulation of neuron projection development / early endosome membrane / positive regulation of cytosolic calcium ion concentration / cytoplasmic vesicle / chemical synaptic transmission / learning or memory / membrane raft / signaling receptor binding / neuronal cell body / synapse / positive regulation of gene expression / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / cell surface / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 21.0 Å | |||||||||
![]() | Matoba K / Mihara E / Tamura-Kawakami K / Hirai H / Thompson S / Iwasaki K / Takagi J | |||||||||
![]() | ![]() Title: Conformational Freedom of the LRP6 Ectodomain Is Regulated by N-glycosylation and the Binding of the Wnt Antagonist Dkk1. Authors: Kyoko Matoba / Emiko Mihara / Keiko Tamura-Kawakami / Naoyuki Miyazaki / Shintaro Maeda / Hidenori Hirai / Samuel Thompson / Kenji Iwasaki / Junichi Takagi / ![]() Abstract: 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. ...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. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 28.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.2 KB 20.2 KB | Display Display | ![]() |
Images | ![]() | 70.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 374.7 KB | Display | ![]() |
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Full document | ![]() | 374.2 KB | Display | |
Data in XML | ![]() | 5.9 KB | Display | |
Data in CIF | ![]() | 6.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5gjeMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 2.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : Human LRP6 ectodomain complexed with full length of Dkk1
+Supramolecule #1: Human LRP6 ectodomain complexed with full length of Dkk1
+Supramolecule #2: LRP6 ectodomain
+Supramolecule #3: Human Dickkopf-related protein1
+Macromolecule #1: Low-density lipoprotein receptor-related protein 6
+Macromolecule #2: Low-density lipoprotein receptor-related protein 6
+Macromolecule #3: Dickkopf-related protein 1
+Macromolecule #4: N-ACETYL-D-GLUCOSAMINE
+Macromolecule #5: PHOSPHATE ION
+Macromolecule #6: ALPHA-L-FUCOSE
+Macromolecule #7: GLYCEROL
+Macromolecule #8: water
-Experimental details
-Structure determination
Method | negative staining |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.2 |
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Staining | Type: NONE / Material: Uranyl acetate |
Grid | Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE |
Details | This sample was monodisperse. |
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Electron microscopy
Microscope | HITACHI H-9500SD |
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Image recording | Film or detector model: TVIPS TEMCAM-F224 (2k x 2k) / Digitization - Dimensions - Width: 2048 pixel / Digitization - Dimensions - Height: 2048 pixel / Digitization - Sampling interval: 24.0 µm / Average exposure time: 2.0 sec. / Average electron dose: 20.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: LAB6 |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.8 mm / Nominal magnification: 80000 |
Sample stage | Specimen holder model: SIDE ENTRY, EUCENTRIC |