10RJ

Heparin-induced cis tetrameric complex of VEGF, VEGFR2 and Neuropilin 1

This is a non-PDB format compatible entry.

Summary for 10RJ

• Entry DOI: 10.2210/pdb10rj/pdb
• EMDB information: 75408
• Descriptor: Neuropilin-1, Isoform VEGF-1 of Vascular endothelial growth factor A, long form, Vascular endothelial growth factor receptor 2, ... (7 entities in total)
• Functional Keywords: vegf, vegfr, neuropilin, signaling protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 12
• Total formula weight: 822426.57

Authors

Chen, L.,Bai, X.,Zhang, X. (deposition date: 2026-02-03, release date: 2026-06-10, Last modification date: 2026-07-29)

Primary citation

Chen, L.,Sun, Z.,Qiao, J.,Bai, X.C.,Zhang, X.
Mechanisms of VEGFR2 activation by VEGF, neuropilin, and heparin.
Sci Adv, 12:eaeg6323-eaeg6323, 2026

PubMed 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-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.

PubMed: 42455955
DOI: 10.1126/sciadv.aeg6323

Experimental method

ELECTRON MICROSCOPY (3.34 Å)