+Open data
-Basic information
Entry | Database: PDB / ID: 8tzo | ||||||||||||
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Title | Structure of human Wnt7a bound to WLS and CALR | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN | ||||||||||||
Function / homology | Function and homology information postsynapse assembly / positive regulation of excitatory synapse assembly / regulation of axon diameter / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / Calnexin/calreticulin cycle / asymmetric protein localization involved in cell fate determination / excitatory synapse assembly / cerebellar granule cell differentiation ...postsynapse assembly / positive regulation of excitatory synapse assembly / regulation of axon diameter / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / Calnexin/calreticulin cycle / asymmetric protein localization involved in cell fate determination / excitatory synapse assembly / cerebellar granule cell differentiation / cytolytic granule / positive regulation of Wnt protein secretion / lens fiber cell development / synaptic vesicle recycling / positive regulation of dendritic cell chemotaxis / WNT ligand biogenesis and trafficking / oviduct development / cortical granule / Assembly of Viral Components at the Budding Site / negative regulation of trophoblast cell migration / ATF6 (ATF6-alpha) activates chaperone genes / central nervous system vasculogenesis / cell proliferation in forebrain / negative regulation of retinoic acid receptor signaling pathway / cellular response to electrical stimulus / endoplasmic reticulum quality control compartment / complement component C1q complex binding / uterus morphogenesis / nuclear receptor-mediated glucocorticoid signaling pathway / secondary palate development / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / regulation of meiotic nuclear division / embryonic axis specification / cementum mineralization / response to glycoside / sequestering of calcium ion / somatic stem cell division / sarcoplasmic reticulum lumen / protein folding in endoplasmic reticulum / presynapse assembly / hormone binding / sex differentiation / positive regulation of epithelial cell proliferation involved in wound healing / hindbrain development / Wnt-protein binding / stem cell development / nuclear export signal receptor activity / negative regulation of intracellular steroid hormone receptor signaling pathway / establishment of blood-brain barrier / cardiac muscle cell differentiation / molecular sequestering activity / exocrine pancreas development / neurotransmitter secretion / frizzled binding / dendritic spine morphogenesis / dorsal/ventral pattern formation / embryonic forelimb morphogenesis / Class B/2 (Secretin family receptors) / embryonic hindlimb morphogenesis / positive regulation of synapse assembly / wound healing, spreading of epidermal cells / Wnt signaling pathway, planar cell polarity pathway / anterior/posterior axis specification / protein maturation by protein folding / Scavenging by Class F Receptors / Scavenging by Class A Receptors / regulation of postsynapse organization / cortical actin cytoskeleton organization / midbrain development / regulation of synaptic vesicle exocytosis / embryonic digit morphogenesis / cartilage condensation / nuclear androgen receptor binding / organelle membrane / establishment of cell polarity / cell fate commitment / cellular response to lithium ion / response to testosterone / somatic stem cell population maintenance / positive regulation of excitatory postsynaptic potential / mesoderm formation / regulation of presynapse assembly / protein localization to nucleus / positive regulation of Wnt signaling pathway / negative regulation of neuron differentiation / smooth endoplasmic reticulum / canonical Wnt signaling pathway / endomembrane system / chondrocyte differentiation / positive regulation of cell cycle / ERAD pathway / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of phagocytosis / protein folding chaperone / cellular response to transforming growth factor beta stimulus / endocytic vesicle lumen / positive regulation of protein metabolic process / protein export from nucleus / positive regulation of endothelial cell migration / endoplasmic reticulum-Golgi intermediate compartment membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||
Authors | Qi, X. / Hu, Q. / Li, X. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Cell / Year: 2023 Title: Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling. Authors: Xiaofeng Qi / Qinli Hu / Nadia Elghobashi-Meinhardt / Tao Long / Hongwen Chen / Xiaochun Li / Abstract: Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility ...Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECK engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8tzo.cif.gz | 236.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8tzo.ent.gz | 181.7 KB | Display | PDB format |
PDBx/mmJSON format | 8tzo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tz/8tzo ftp://data.pdbj.org/pub/pdb/validation_reports/tz/8tzo | HTTPS FTP |
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-Related structure data
Related structure data | 41764MC 8tzpC 8tzsC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 3 types, 3 molecules ABC
#1: Protein | Mass: 39062.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WNT7A / Production host: Homo sapiens (human) / References: UniProt: O00755 |
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#2: Protein | Mass: 62317.973 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WLS / Production host: Homo sapiens (human) / References: UniProt: Q5T9L3 |
#3: Protein | Mass: 48198.379 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P27797 |
-Sugars , 1 types, 1 molecules
#4: Polysaccharide | alpha-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D- ...alpha-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Type: oligosaccharide / Mass: 1235.105 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source |
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-Non-polymers , 3 types, 3 molecules
#5: Chemical | ChemComp-PAM / |
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#6: Chemical | ChemComp-POV / ( |
#7: Chemical | ChemComp-CA / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Wnt7a-WLS-CALR Complex / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 276377 / Symmetry type: POINT | ||||||||||||||||||||||||
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