title: Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A.
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 Zn2+, Co2+ or Cu2+ 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 Co2+, Cd2+ or Cu2+. 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.
authors.affiliation: UMR 8015 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-François
authors.identifier: http://orcid.org/0000-0002-8448-1491
authors.initials: JF
authors.lastname: Gaucher
authors.affiliation: UMR 8638 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Reille-Seroussi
authors.affiliation: UMR 8638 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gagey-Eilstein
authors.affiliation: UMR 8638 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Broussy
authors.affiliation: UMR 8015 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Coric
authors.affiliation: UMR 8015 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Bili
authors.initials: B
authors.lastname: Seijo
authors.affiliation: UMR 8015 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Marie-Bernard
authors.initials: MB
authors.lastname: Lascombe
authors.affiliation: UMR 8638 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Gautier
authors.affiliation: UMR 8638 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Wang-Quing
authors.initials: WQ
authors.lastname: Liu
authors.affiliation: UMR 8638 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Huguenot
authors.affiliation: Centre de Recherche Insulaire et Observatoire de l'Environnement USR CNRS 3278 CRIOBE, Université de Perpignan Via Domitia, Perpignan, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Inguimbert
authors.affiliation: UMR 8015 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Bouaziz
authors.affiliation: UMR 8638 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.|UF Pharmacocinétique et Pharmacochimie, hôpital Cochin, AP-HP, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vidal
authors.affiliation: UMR 8015 CNRS - Université Paris Descartes, Faculté de Pharmacie, Sorbonne Paris Cité, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Broutin
mesh_terms: D001665:Binding Sites; D002413:Cations, Divalent / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1