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 chro-
matography 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.
https://hal-univ-perp.archives-ouvertes.fr/hal-01439207
Contributeur : Dorian Miler
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Soumis le : mercredi 18 janvier 2017 - 13:16:59
Dernière modification le : jeudi 11 janvier 2018 - 06:26:02
Document(s) archivé(s) le : mercredi 19 avril 2017 - 14:07:06
Jean-François Gaucher, Marie 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, Public Library of Science, 2016, 〈10.1371/journal. pone.0167755〉. 〈hal-01439207〉