CRYSTALLIZATION OF THE RECEPTOR-BINDING DOMAIN OF VASCULAR ENDOTHELIAL GROWTH-FACTOR

Vascular endothelial growth factor (VEGF) is a potent angiogenic facto r with a unique specificity for vascular endothelial cells. In additio n to its role in vasculogenesis and embryonic angiogenesis, VEGF is im plicated in pathologic neovascularization associated with tumors and d iabetic retinopathy. Four different constructs of a short variant of V EGF sufficient for receptor binding were overexpressed in Escherichia coli, refolded, purified, and crystallized in five different space gro ups. In order to facilitate the production of heavy atom derivatives, single cysteine mutants were designed based on the crystal structure o f platelet-derived growth factor. A construct consisting of residues 8 to 109 was crystallized in space group P2(1), with cell parameters a = 55.6 Angstrom, b = 60.4 Angstrom, c = 77.7 Angstrom, beta = 90.0 deg rees, and four monomers in the asymmetric unit. Native and derivative data were collected for two of the cysteine mutants as well as for wil d-type VEGF. (C) 1996 Wiley-Liss, Inc.