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

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Bioengineering

Life Sciences [q-bio] / Pharmaceutical sciences

Complete list of metadatas

Cited literature [74 references] Display Hide Download

https://hal-univ-perp.archives-ouvertes.fr/hal-01439207
Contributor : Dorian Miler <>
Submitted on : Wednesday, January 18, 2017 - 1:16:59 PM
Last modification on : Thursday, July 11, 2019 - 2:10:08 PM
Long-term archiving on : Wednesday, April 19, 2017 - 2:07:06 PM

journal.pone.0167755.pdf

Publisher files allowed on an open archive

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

File

Identifiers

Collections

Citation

Export

Metrics

284

191

Contact

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

File

Identifiers

Collections

Citation

Export

Share

Metrics

284

191

Contact