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

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

doi:10.1371/journal. pone.0167755

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

Jean-François Gaucher ¹ Marie Reille-Seroussi ² Nathalie Gagey-Eilstein ² Sylvain Broussy ² Pascale Coric ¹ Bili Seijo ¹ Marie-Bernard Lascombe ¹ Benoit Gautier ² Wang-Quing Liu ² Florent Huguenot ² Nicolas Inguimbert ³ Serge Bouaziz ¹ Michel Vidal ^{2, 4} Isabelle Broutin ¹

1 LCRB - UMR 8015 - Laboratoire de cristallographie et RMN biologiques

2 COMETE - UMR 8638 - Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale

3 CRIOBE - Centre de recherches insulaires et observatoire de l'environnement

4 PMC - UMR_S 648 - Pharmacochimie Moléculaire et Cellulaire

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.

Type de document :

Article dans une revue

PLoS ONE, Public Library of Science, 2016, 〈10.1371/journal. pone.0167755〉

Domaine :

Sciences du Vivant [q-bio] / Ingénierie biomédicale

Sciences du Vivant [q-bio] / Sciences pharmaceutiques

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https://hal-univ-perp.archives-ouvertes.fr/hal-01439207
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Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A

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