Investigating the effect of VEGF glycosylation on glycosaminoglycan binding and protein unfolding.
VEGF165 binding to endothelial cells is potentiated by glycosaminoglycans (GAGs). Here, we have investigated the impact of VEGF165 N-glycosylation on GAG binding. Although glycosylated VEGF165 bound to heparin with only slightly higher affinity than non-glycosylated VEGF165, the natural ligand heparan sulfate induced a conformational change only in the glycosylated protein. Unfolding studies of the VEGF proteins indicated a stabilising effect of heparin on the growth factor structure.
Brandner
Barbara
B
Institute of Pharmaceutical Sciences, University of Graz, A-8010 Graz, Austria.
Kurkela
Riitta
R
Vihko
Pirkko
P
Kungl
Andreas J
AJ
D000818:Animals; D002151:Calorimetry; D002460:Cell Line; D002942:Circular Dichroism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry*; D006031:Glycosylation; D006133:Growth Substances; D006493:Heparin / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry; D006801:Humans; D007313:Insecta; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000378:metabolism
D018076:DNA, Complementary; D006025:Glycosaminoglycans; D006133:Growth Substances; D006493:Heparin; D006497:Heparan Sulfate; D008024:Ligands; D042461:Vascular Endothelial Growth Factor A