PDBsum entry 1vgh

Growth factor

PDB id: 1vgh

Contents

Protein chain

55 a.a. *

* Residue conservation analysis

PDB id:

1vgh

Name:

Growth factor

Title:

Heparin-binding domain from vascular endothelial growth factor, nmr, 20 structures

Structure:

Vascular endothelial growth factor-165. Chain: a. Fragment: heparin-binding domain. Synonym: vegf-165. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

20 models

Authors:

W.J.Fairbrother,M.A.Champe,H.W.Christinger,B.A.Keyt,M.A.Starovasnik

Key ref:

W.J.Fairbrother et al. (1998). Solution structure of the heparin-binding domain of vascular endothelial growth factor. Structure, 6, 637-648. PubMed id: 9634701 DOI: 10.1016/S0969-2126(98)00065-3

Date:

17-Dec-97 Release date: 08-Apr-98

Protein chain

P15692  (VEGFA_HUMAN) -  Vascular endothelial growth factor A, long form from Homo sapiens

Seq: 395 a.a.

Struc: 55 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1016/S0969-2126(98)00065-3

Structure 6:637-648 (1998)

PubMed id: 9634701

Solution structure of the heparin-binding domain of vascular endothelial growth factor.

W.J.Fairbrother, M.A.Champe, H.W.Christinger, B.A.Keyt, M.A.Starovasnik.

ABSTRACT

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.

Selected figure(s)

Figure 7.
Figure 7. The solvent-accessible molecular surface of the minimized mean structure of VEGF[55] color coded according to electrostatic surface potential; red, -10 kT; white, 0 kT; and blue, +10 kT. The positions of charged sidechains are labeled. The two views are related by a 180° rotation about the vertical axis. The figure was produced using the program GRASP [70].

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 637-648) copyright 1998.

Figure was selected by an automated process.