PLoS ONE (Jan 2016)

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
https://doi.org/10.1371/journal.pone.0167755
Journal volume & issue
Vol. 11, no. 12
p. e0167755

Abstract

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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.