Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A.
Jean-François GaucherMarie Reille-SeroussiNathalie Gagey-EilsteinSylvain BroussyPascale CoricBili SeijoMarie-Bernard LascombeBenoit GautierWang-Quing LiuFlorent HuguenotNicolas InguimbertSerge BouazizMichel VidalIsabelle BroutinPublished in: PloS one (2016)
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.
Keyphrases
- endothelial cells
- high glucose
- vascular endothelial growth factor
- binding protein
- aqueous solution
- diabetic rats
- magnetic resonance
- high throughput
- drug induced
- high resolution
- mass spectrometry
- health risk
- high speed
- health risk assessment
- cystic fibrosis
- oxidative stress
- escherichia coli
- biofilm formation
- single molecule
- quantum dots