Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A - Archive ouverte HAL Access content directly
Journal Articles PLoS ONE Year : 2016

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

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Abstract

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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hal-01439207 , version 1 (18-01-2017)

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Jean-François Gaucher, Marie Reille-Seroussi Reille-Seroussi, Nathalie Gagey-Eilstein, Sylvain Broussy, Pascale Coric, et al.. Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A. PLoS ONE, 2016, 11 (12), pp.e0167755. ⟨10.1371/journal.pone.0167755⟩. ⟨hal-01439207⟩
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