+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30827 | |||||||||
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Title | Human Wntless in complex with Wnt3a | |||||||||
Map data | 2.2_angstrom_map for WLS-Wnt3a complex | |||||||||
Sample |
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Keywords | Wnt signaling / Wnt secretion / WLS / Wnt3a / cryo-EM / palmitoleoylation / membrane protein | |||||||||
Function / homology | Function and homology information Wnt signaling pathway involved in forebrain neuroblast division / positive regulation of dermatome development / calcium ion transmembrane transport via low voltage-gated calcium channel / positive regulation of collateral sprouting in absence of injury / positive regulation of mesodermal cell fate specification / paraxial mesodermal cell fate commitment / axis elongation involved in somitogenesis / cell proliferation in midbrain / spinal cord association neuron differentiation / Wnt protein secretion ...Wnt signaling pathway involved in forebrain neuroblast division / positive regulation of dermatome development / calcium ion transmembrane transport via low voltage-gated calcium channel / positive regulation of collateral sprouting in absence of injury / positive regulation of mesodermal cell fate specification / paraxial mesodermal cell fate commitment / axis elongation involved in somitogenesis / cell proliferation in midbrain / spinal cord association neuron differentiation / Wnt protein secretion / Formation of the posterior neural plate / COP9 signalosome assembly / Wnt-Frizzled-LRP5/6 complex / positive regulation of cell-cell adhesion mediated by cadherin / positive regulation of Wnt protein secretion / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / synaptic vesicle recycling / WNT ligand biogenesis and trafficking / Signaling by RNF43 mutants / positive regulation of cardiac muscle cell differentiation / cell proliferation in forebrain / negative regulation of axon extension involved in axon guidance / secondary palate development / Specification of the neural plate border / cementum mineralization / somatic stem cell division / cardiac muscle cell fate commitment / co-receptor binding / presynapse assembly / non-canonical Wnt signaling pathway / hindbrain development / positive regulation of skeletal muscle tissue development / negative regulation of dopaminergic neuron differentiation / Wnt-protein binding / midbrain dopaminergic neuron differentiation / dorsal/ventral neural tube patterning / regulation of postsynapse to nucleus signaling pathway / exocrine pancreas development / mammary gland development / post-anal tail morphogenesis / positive regulation of neural precursor cell proliferation / frizzled binding / Class B/2 (Secretin family receptors) / positive regulation of hepatocyte proliferation / myoblast differentiation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / anterior/posterior axis specification / inner ear morphogenesis / midbrain development / regulation of synapse organization / negative regulation of fat cell differentiation / organelle membrane / B cell proliferation / fat cell differentiation / heart looping / Formation of paraxial mesoderm / skeletal muscle cell differentiation / positive regulation of receptor internalization / hemopoiesis / mesoderm formation / regulation of presynapse assembly / positive regulation of Wnt signaling pathway / cell fate commitment / canonical Wnt signaling pathway / endomembrane system / Transcriptional and post-translational regulation of MITF-M expression and activity / regulation of microtubule cytoskeleton organization / positive regulation of B cell proliferation / cellular response to retinoic acid / Regulation of FZD by ubiquitination / extracellular matrix organization / axon guidance / positive regulation of cytokine production / cytokine activity / TCF dependent signaling in response to WNT / hippocampus development / positive regulation of protein localization to plasma membrane / intracellular protein transport / trans-Golgi network / modulation of chemical synaptic transmission / neuron differentiation / platelet aggregation / Wnt signaling pathway / negative regulation of neurogenesis / Golgi lumen / osteoblast differentiation / endocytic vesicle membrane / protein localization / positive regulation of canonical Wnt signaling pathway / negative regulation of neuron projection development / positive regulation of peptidyl-serine phosphorylation / presynapse / heart development / early endosome membrane / cytoplasmic vesicle / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / transcription by RNA polymerase II / cell population proliferation / transcription coactivator activity Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||
Authors | Zhong Q / Zhao Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2021 Title: Cryo-EM structure of human Wntless in complex with Wnt3a. Authors: Qing Zhong / Yanyu Zhao / Fangfei Ye / Zaiyu Xiao / Gaoxingyu Huang / Meng Xu / Yuanyuan Zhang / Xiechao Zhan / Ke Sun / Zhizhi Wang / Shanshan Cheng / Shan Feng / Xiuxiu Zhao / Jizhong ...Authors: Qing Zhong / Yanyu Zhao / Fangfei Ye / Zaiyu Xiao / Gaoxingyu Huang / Meng Xu / Yuanyuan Zhang / Xiechao Zhan / Ke Sun / Zhizhi Wang / Shanshan Cheng / Shan Feng / Xiuxiu Zhao / Jizhong Zhang / Peilong Lu / Wenqing Xu / Qiang Zhou / Dan Ma / Abstract: Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas ...Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report the cryo-EM structure of human WLS in complex with Wnt3a, the most widely studied Wnt, at 2.2 Å resolution. The transmembrane domain of WLS bears a GPCR fold, with a conserved core cavity and a lateral opening. Wnt3a interacts with WLS at multiple interfaces, with the lipid moiety on Wnt3a traversing a hydrophobic tunnel of WLS transmembrane domain and inserting into membrane. A β-hairpin of Wnt3a containing the conserved palmitoleoylation site interacts with WLS extensively, which is crucial for WLS-mediated Wnt secretion. The flexibility of the Wnt3a loop/hairpin regions involved in the multiple binding sites indicates induced fit might happen when Wnts are bound to different binding partners. Our findings provide important insights into the molecular mechanism of Wnt palmitoleoylation, secretion and signaling. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30827.map.gz | 482.7 MB | EMDB map data format | |
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Header (meta data) | emd-30827-v30.xml emd-30827.xml | 16.4 KB 16.4 KB | Display Display | EMDB header |
Images | emd_30827.png | 60.5 KB | ||
Filedesc metadata | emd-30827.cif.gz | 6.2 KB | ||
Others | emd_30827_additional_1.map.gz | 28.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30827 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30827 | HTTPS FTP |
-Validation report
Summary document | emd_30827_validation.pdf.gz | 471 KB | Display | EMDB validaton report |
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Full document | emd_30827_full_validation.pdf.gz | 470.6 KB | Display | |
Data in XML | emd_30827_validation.xml.gz | 7.8 KB | Display | |
Data in CIF | emd_30827_validation.cif.gz | 9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30827 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30827 | HTTPS FTP |
-Related structure data
Related structure data | 7drtMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30827.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | 2.2_angstrom_map for WLS-Wnt3a complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.5435 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: 3.2 angstrom map for WLS-Wnt3a complex
File | emd_30827_additional_1.map | ||||||||||||
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Annotation | 3.2_angstrom_map for WLS-Wnt3a complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Human Wntless in complex with Wnt3a
+Supramolecule #1: Human Wntless in complex with Wnt3a
+Supramolecule #2: Wnt3a
+Supramolecule #3: Wntless
+Macromolecule #1: Protein Wnt-3a
+Macromolecule #2: Protein wntless homolog
+Macromolecule #4: PALMITOLEIC ACID
+Macromolecule #5: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #6: CHOLESTEROL
+Macromolecule #7: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #8: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0.6) / Number images used: 8482332 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |