+Open data
-Basic information
Entry | Database: PDB / ID: 7drt | ||||||
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Title | Human Wntless in complex with Wnt3a | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Wnt signaling / Wnt secretion / WLS / Wnt3a / cryo-EM / palmitoleoylation | ||||||
Function / homology | Function and homology information Wnt signaling pathway involved in forebrain neuroblast division / positive regulation of dermatome development / axis elongation involved in somitogenesis / 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 / cell proliferation in midbrain / spinal cord association neuron differentiation / Formation of the posterior neural plate ...Wnt signaling pathway involved in forebrain neuroblast division / positive regulation of dermatome development / axis elongation involved in somitogenesis / 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 / cell proliferation in midbrain / spinal cord association neuron differentiation / Formation of the posterior neural plate / Wnt protein secretion / COP9 signalosome assembly / Wnt-Frizzled-LRP5/6 complex / positive regulation of Wnt protein secretion / positive regulation of cell-cell adhesion mediated by cadherin / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / synaptic vesicle recycling / Signaling by RNF43 mutants / WNT ligand biogenesis and trafficking / 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 / non-canonical Wnt signaling pathway / co-receptor binding / cardiac muscle cell fate commitment / presynapse assembly / hindbrain development / positive regulation of skeletal muscle tissue development / Wnt-protein binding / negative regulation of dopaminergic neuron differentiation / 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 / frizzled binding / positive regulation of neural precursor cell proliferation / positive regulation of hepatocyte proliferation / Class B/2 (Secretin family receptors) / Disassembly of the destruction complex and recruitment of AXIN to the membrane / myoblast differentiation / anterior/posterior axis specification / inner ear morphogenesis / midbrain development / organelle membrane / cell fate commitment / regulation of synapse organization / negative regulation of fat cell differentiation / 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 / Transcriptional and post-translational regulation of MITF-M expression and activity / canonical Wnt signaling pathway / endomembrane system / regulation of microtubule cytoskeleton organization / cellular response to retinoic acid / positive regulation of B cell proliferation / Regulation of FZD by ubiquitination / positive regulation of protein localization to plasma membrane / extracellular matrix organization / positive regulation of cytokine production / TCF dependent signaling in response to WNT / cytokine activity / axon guidance / hippocampus development / intracellular protein transport / trans-Golgi network / modulation of chemical synaptic transmission / neuron differentiation / Wnt signaling pathway / platelet aggregation / negative regulation of neurogenesis / Golgi lumen / osteoblast differentiation / positive regulation of canonical Wnt signaling pathway / endocytic vesicle membrane / positive regulation of peptidyl-serine phosphorylation / protein localization / negative regulation of neuron projection development / early endosome membrane / presynapse / heart development / positive regulation of canonical NF-kappaB signal transduction / cytoplasmic vesicle / transcription coactivator activity / in utero embryonic development / cell population proliferation / transcription by RNA polymerase II Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.2 Å | ||||||
Authors | Zhong, Q. / Zhao, Y. / Ye, F. / Xiao, Z. / Huang, G. / Zhang, Y. / Lu, P. / Xu, W. / Zhou, Q. / Ma, D. | ||||||
Funding support | China, 1items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7drt.cif.gz | 157.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7drt.ent.gz | 128.4 KB | Display | PDB format |
PDBx/mmJSON format | 7drt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7drt_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7drt_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7drt_validation.xml.gz | 32.3 KB | Display | |
Data in CIF | 7drt_validation.cif.gz | 45.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dr/7drt ftp://data.pdbj.org/pub/pdb/validation_reports/dr/7drt | HTTPS FTP |
-Related structure data
Related structure data | 30827MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 39421.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WNT3A / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P56704 |
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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, C1orf139, GPR177, UNQ85/PRO18667 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q5T9L3 |
-Sugars , 1 types, 1 molecules
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
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-Non-polymers , 5 types, 15 molecules
#4: Chemical | ChemComp-PAM / | ||||||
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#5: Chemical | #6: Chemical | ChemComp-CLR / | #7: Chemical | ChemComp-LPE / | #8: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | N |
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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
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
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 / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software | Name: RELION / Version: 3.0.6 / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 2.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 8482332 / Symmetry type: POINT |