1vgh
From Proteopedia
(New page: 200px<br /> <applet load="1vgh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vgh" /> '''HEPARIN-BINDING DOMAIN FROM VASCULAR ENDOTH...) |
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'''HEPARIN-BINDING DOMAIN FROM VASCULAR ENDOTHELIAL GROWTH FACTOR, NMR, 20 STRUCTURES'''<br /> | '''HEPARIN-BINDING DOMAIN FROM VASCULAR ENDOTHELIAL GROWTH FACTOR, NMR, 20 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1VGH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1VGH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VGH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Champe, M | + | [[Category: Champe, M A.]] |
| - | [[Category: Christinger, H | + | [[Category: Christinger, H W.]] |
| - | [[Category: Fairbrother, W | + | [[Category: Fairbrother, W J.]] |
| - | [[Category: Keyt, B | + | [[Category: Keyt, B A.]] |
| - | [[Category: Starovasnik, M | + | [[Category: Starovasnik, M A.]] |
[[Category: angiogenesis]] | [[Category: angiogenesis]] | ||
[[Category: growth factor]] | [[Category: growth factor]] | ||
[[Category: heparin-binding]] | [[Category: heparin-binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:35:01 2008'' |
Revision as of 13:35, 21 February 2008
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HEPARIN-BINDING DOMAIN FROM VASCULAR ENDOTHELIAL GROWTH FACTOR, NMR, 20 STRUCTURES
Contents |
Overview
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.
Disease
Known disease associated with this structure: Diabetic retinopathy, NIDDM-related, susceptibility to OMIM:[192240]
About this Structure
1VGH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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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