1VPF

STRUCTURE OF HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR

Summary for 1VPF

• Entry DOI: 10.2210/pdb1vpf/pdb
• Descriptor: VASCULAR ENDOTHELIAL GROWTH FACTOR (2 entities in total)
• Functional Keywords: growth factor, cystine knot, angiogenesis, vasculogenesis
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P15692
• Total number of polymer chains: 4
• Total formula weight: 47794.72

Authors

Muller, Y.A.,De Vos, A.M. (deposition date: 1997-04-08, release date: 1998-04-08, Last modification date: 2024-10-09)

Primary citation

Muller, Y.A.,Li, B.,Christinger, H.W.,Wells, J.A.,Cunningham, B.C.,de Vos, A.M.
Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site.
Proc.Natl.Acad.Sci.USA, 94:7192-7197, 1997

PubMed Abstract: Vascular endothelial growth factor (VEGF) is a homodimeric member of the cystine knot family of growth factors, with limited sequence homology to platelet-derived growth factor (PDGF) and transforming growth factor beta2 (TGF-beta). We have determined its crystal structure at a resolution of 2.5 A, and identified its kinase domain receptor (KDR) binding site using mutational analysis. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended. The dimerization mode of VEGF is similar to that of PDGF and very different from that of TGF-beta. Mutational analysis of VEGF reveals that symmetrical binding sites for KDR are located at each pole of the VEGF homodimer. Each site contains two functional "hot spots" composed of binding determinants presented across the subunit interface. The two most important determinants are located within the largest hot spot on a short, three-stranded sheet that is conserved in PDGF and TGF-beta. Functional analysis of the binding epitopes for two receptor-blocking antibodies reveal different binding determinants near each of the KDR binding hot spots.

PubMed: 9207067
DOI: 10.1073/pnas.94.14.7192

Experimental method

X-RAY DIFFRACTION (2.5 Å)