Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A

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Gaucher, Jean-François | Reille-Seroussi, Marie, Reille-Seroussi | Gagey-Eilstein, Nathalie | Broussy, Sylvain | Coric, Pascale | Seijo, Bili | Lascombe, Marie-Bernard | Gautier, Benoit | Liu, Wang-Quing | Huguenot, Florent | Inguimbert, Nicolas | Bouaziz, Serge | Vidal, Michel | Broutin, Isabelle

Edité par CCSD ; Public Library of Science -

International audience. Angiogenesis is tightly regulated through the binding of vascular endothelial growth factors (VEGFs) to their receptors (VEGFRs). In this context, we showed that human VEGFR1 domain 2 crystallizes in the presence of Zn 2+ , Co 2+ or Cu 2+ as a dimer that forms via metal-ion interactions and interlocked hydrophobic surfaces. SAXS, NMR and size exclusion chromatography analyses confirm the formation of this dimer in solution in the presence of Co 2+ , Cd 2+ or Cu 2+ . Since the metal-induced dimerization masks the VEGFs binding surface, we investigated the ability of metal ions to displace the VEGF-A binding to hVEGFR1: using a competition assay, we evidenced that the metals displaced the VEGF-A binding to hVEGFR1 extracellular domain binding at micromolar level.

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