2vgh
HEPARIN-BINDING DOMAIN FROM VASCULAR ENDOTHELIAL GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE
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OverviewOverview
BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial, cell-specific mitogen and is a potent angiogenic and vascular, permeabilizing factor. VEGF is also an important mediator of pathological, angiogenesis associated with cancer, rheumatoid arthritis and, proliferative retinopathy. The binding of VEGF to its two known receptors, KDR and Flt-1, is modulated by cell-surface-associated heparin-like, glycosaminoglycans and exogenous heparin or heparan sulfate. Heparin, binding to VEGF165, the most abundantly expressed isoform of VEGF, has, been localized to the carboxy-terminal 55 residues; plasmin cleavage of, VEGF165 yields a homodimeric 110-residue amino-terminal receptor-binding, domain (VEGF110) and two 55-residue carboxy-terminal heparin-binding, fragments. The endothelial cell mitogenic potency of VEGF110 is decreased, significantly relative to VEGF165, indicating that the heparin-binding, domains are critical for stimulating endothelial cell proliferation., RESULTS: The solution structure of the 55-residue heparin-binding domain, of VEGF165 has been solved using data from two-dimensional homonuclear and, three-dimensional heteronuclear NMR spectroscopy. The structure has two, subdomains, each containing two disulfide bridges and a short two-stranded, antiparallel beta sheet; the carboxy-terminal subdomain also contains a, short alpha helix. Hydrophobic interactions are limited to sidechains, packing against the disulfide bridges. CONCLUSIONS: The heparin-binding, domain of VEGF has no significant sequence or structural similarity to any, known proteins and thus represents a novel heparin-binding domain. Most of, the positively charged amino acid sidechains are localized on one side of, the carboxy-terminal subdomain or on an adjacent disordered loop in the, amino-terminal subdomain. The observed distribution of surface charges, suggests that these residues constitute a heparin interaction site.
DiseaseDisease
Known disease associated with this structure: Diabetic retinopathy, NIDDM-related, susceptibility to OMIM:[192240]
About this StructureAbout this Structure
2VGH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the heparin-binding domain of vascular endothelial growth factor., Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA, Structure. 1998 May 15;6(5):637-48. PMID:9634701
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