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Yorodumi- PDB-10rj: Heparin-induced cis tetrameric complex of VEGF, VEGFR2 and Neurop... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 10rj | ||||||||||||||||||||||||
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| Title | Heparin-induced cis tetrameric complex of VEGF, VEGFR2 and Neuropilin 1 | ||||||||||||||||||||||||
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Keywords | SIGNALING PROTEIN / VEGF / VEGFR / neuropilin | ||||||||||||||||||||||||
| Function / homology | Function and homology informationpositive regulation of lymphangiogenesis / VEGF-A complex / VEGF ligand-receptor interactions / VEGF binds to VEGFR leading to receptor dimerization / blood vessel endothelial cell differentiation / Neuropilin interactions with VEGF and VEGFR / bone trabecula formation / post-embryonic camera-type eye morphogenesis / cell migration involved in coronary vasculogenesis / trigeminal nerve morphogenesis ...positive regulation of lymphangiogenesis / VEGF-A complex / VEGF ligand-receptor interactions / VEGF binds to VEGFR leading to receptor dimerization / blood vessel endothelial cell differentiation / Neuropilin interactions with VEGF and VEGFR / bone trabecula formation / post-embryonic camera-type eye morphogenesis / cell migration involved in coronary vasculogenesis / trigeminal nerve morphogenesis / VEGFR2 mediated cell proliferation / Signal transduction by L1 / dichotomous subdivision of terminal units involved in salivary gland branching / regulation of bone development / regulation of hematopoietic progenitor cell differentiation / regulation of axon extension involved in axon guidance / regulation of endothelial cell differentiation / negative regulation of axon extension involved in axon guidance / basal dendrite development / otic placode development / CRMPs in Sema3A signaling / Sema3A PAK dependent Axon repulsion / basal dendrite arborization / regulation of endothelial cell proliferation / positive regulation of smooth muscle cell chemotaxis / retina vasculature morphogenesis in camera-type eye / vestibulocochlear nerve structural organization / dorsal root ganglion morphogenesis / lymphangiogenesis / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / sensory neuron axon guidance / basophil chemotaxis / lymph vessel morphogenesis / positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway / positive regulation of nitric oxide-cGMP mediated signal transduction / cellular stress response to acid chemical / : / facial nerve structural organization / trigeminal nerve structural organization / branchiomotor neuron axon guidance / vascular endothelial growth factor receptor 1 binding / negative regulation of adherens junction organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus / protein localization to early endosome / post-embryonic camera-type eye development / primitive erythrocyte differentiation / retina vasculature development in camera-type eye / positive regulation of mast cell chemotaxis / negative regulation of establishment of endothelial barrier / vascular endothelial growth factor receptor binding / negative regulation of blood-brain barrier permeability / lung vasculature development / VEGF-activated neuropilin signaling pathway / axon extension involved in axon guidance / positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway / motor neuron migration / eye photoreceptor cell development / renal artery morphogenesis / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / positive regulation of signal transduction / cellular response to hydrogen sulfide / endothelium development / endochondral bone growth / coronary vein morphogenesis / cardiac vascular smooth muscle cell development / lymph vessel development / neurofilament / regulation of vascular endothelial growth factor receptor signaling pathway / sympathetic neuron projection extension / mammary gland alveolus development / endocardium development / angiogenesis involved in coronary vascular morphogenesis / postsynapse organization / vascular endothelial growth factor binding / endothelial cell differentiation / vascular endothelial growth factor receptor-2 signaling pathway / endothelial tube morphogenesis / sympathetic ganglion development / negative regulation of axon extension / neural crest cell migration involved in autonomic nervous system development / axonogenesis involved in innervation / bone trabecula morphogenesis / vascular endothelial growth factor receptor activity / positive regulation of axon extension involved in axon guidance / endothelial cell chemotaxis / camera-type eye morphogenesis / positive regulation of protein localization to early endosome / Platelet degranulation / positive regulation of trophoblast cell migration / surfactant homeostasis / positive regulation of long-term neuronal synaptic plasticity / sympathetic nervous system development / retinal ganglion cell axon guidance / positive regulation of vasculogenesis / induction of positive chemotaxis / vascular wound healing / dopaminergic neuron differentiation Similarity search - Function | ||||||||||||||||||||||||
| Biological species | ![]() | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.34 Å | ||||||||||||||||||||||||
Authors | Chen, L. / Bai, X. / Zhang, X. | ||||||||||||||||||||||||
| Funding support | United States, 4items
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Citation | Journal: Sci Adv / Year: 2026Title: Mechanisms of VEGFR2 activation by VEGF, neuropilin, and heparin. Authors: Lianqi Chen / Zhichen Sun / Jian Qiao / Xiao-Chen Bai / Xuewu Zhang / ![]() Abstract: Vascular endothelial growth factor (VEGF) and its receptor VEGFR are master regulators of vasculogenesis and angiogenesis. VEGF activates VEGFR by inducing its dimerization and trans- ...Vascular endothelial growth factor (VEGF) and its receptor VEGFR are master regulators of vasculogenesis and angiogenesis. VEGF activates VEGFR by inducing its dimerization and trans-autophosphorylation. The coreceptor neuropilin (Nrp1 and Nrp2) and heparan sulfate proteoglycan (HSPG) modulate VEGF-VEGFR signaling, but the underlying mechanisms remain incompletely understood. Here we report a cryo-EM structure of the dimeric mouse VEGF-VEGFR2-Nrp1 ectodomain complex with a 2:2:2 stoichiometry, revealing direct Nrp1-VEGFR2 interactions that stabilize the VEGFR2 dimer. We also determined two cryo-EM structures of the VEGF-VEGFR2-Nrp1 complex in the presence of short- or long-chain heparin, which bridges all three proteins and promotes the formation of two distinct tetrameric complexes. Long-chain heparin induces a cis tetrameric complex consistent with receptor clustering on the same cell surface, whereas short-chain heparin promotes a trans tetrameric assembly which might be formed by two dimeric complexes from opposing cells. Our structure-based mutational analyses support the model that both the Nrp1-VEGFR2 interface and the heparin-mediated clustering enhance VEGFR2 signaling. | ||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 10rj.cif.gz | 2 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb10rj.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 10rj.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/0r/10rj ftp://data.pdbj.org/pub/pdb/validation_reports/0r/10rj | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 75408MC ![]() 10riC ![]() 10rkC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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| 1 |
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Components
-Protein , 3 types, 12 molecules FLEKABGHCDIJ
| #1: Protein | Mass: 95312.578 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) / References: UniProt: P97333#2: Protein | Mass: 20787.742 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) / References: UniProt: Q00731#3: Protein | Mass: 84499.039 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human)References: UniProt: P35918, receptor protein-tyrosine kinase |
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-Sugars , 3 types, 16 molecules 
| #4: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Polysaccharide | Type: oligosaccharide / Mass: 8102.604 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Non-polymers , 1 types, 8 molecules 
| #6: Chemical | ChemComp-CA / |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: dimeric complex of VEGF, VEGFR2 and Neuropilin 1 / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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| Molecular weight | Value: 0.8 MDa / Experimental value: NO |
| Source (natural) | Organism: ![]() |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: NITROGEN |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
| 3D reconstruction | Resolution: 3.34 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 105039 / Symmetry type: POINT | ||||||||||||||||
| Refinement | Highest resolution: 3.34 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) |
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United States, 4items
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Homo sapiens (human)
FIELD EMISSION GUN