+Open data
-Basic information
Entry | Database: PDB / ID: 8tzp | ||||||||||||
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Title | Structure of human Wnt7a bound to WLS and RECK | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN | ||||||||||||
Function / homology | Function and homology information regulation of establishment of blood-brain barrier / negative regulation of metalloendopeptidase activity / Wnt protein secretion / blood vessel maturation / positive regulation of Wnt protein secretion / WNT ligand biogenesis and trafficking / Post-translational modification: synthesis of GPI-anchored proteins / metalloendopeptidase inhibitor activity / cementum mineralization / hindbrain development ...regulation of establishment of blood-brain barrier / negative regulation of metalloendopeptidase activity / Wnt protein secretion / blood vessel maturation / positive regulation of Wnt protein secretion / WNT ligand biogenesis and trafficking / Post-translational modification: synthesis of GPI-anchored proteins / metalloendopeptidase inhibitor activity / cementum mineralization / hindbrain development / regulation of extracellular matrix organization / Wnt-protein binding / exocrine pancreas development / embryonic forelimb morphogenesis / Wnt signalosome / sprouting angiogenesis / anterior/posterior axis specification / midbrain development / endopeptidase inhibitor activity / organelle membrane / positive regulation of Wnt signaling pathway / mesoderm formation / endomembrane system / regulation of angiogenesis / canonical Wnt signaling pathway / coreceptor activity / side of membrane / embryo implantation / extracellular matrix organization / negative regulation of cell migration / intracellular protein transport / serine-type endopeptidase inhibitor activity / trans-Golgi network / Wnt signaling pathway / endocytic vesicle membrane / positive regulation of canonical Wnt signaling pathway / early endosome membrane / cytoplasmic vesicle / positive regulation of canonical NF-kappaB signal transduction / early endosome / Golgi membrane / endoplasmic reticulum membrane / Golgi apparatus / endoplasmic reticulum / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.23 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 | 8tzp.cif.gz | 204 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8tzp.ent.gz | 148 KB | Display | PDB format |
PDBx/mmJSON format | 8tzp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8tzp_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8tzp_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8tzp_validation.xml.gz | 37.3 KB | Display | |
Data in CIF | 8tzp_validation.cif.gz | 53 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tz/8tzp ftp://data.pdbj.org/pub/pdb/validation_reports/tz/8tzp | HTTPS FTP |
-Related structure data
Related structure data | 41765MC 8tzoC 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
#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: 106573.461 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RECK / Production host: Homo sapiens (human) / References: UniProt: O95980 |
#4: Chemical | ChemComp-PAM / |
#5: Chemical | ChemComp-POV / ( |
Has ligand of interest | Y |
-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-RECK Complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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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: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 87543 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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