The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 angstrom resolution

The angiogenic molecule placenta growth factor (PlGF) is a member of the cy steine-knot family of growth factors. In this study, a mature isoform of th e human PlGF protein, PlGF-1, was crystallized as a homodimer in the crysta llographic asymmetric unit, and its crystal structure was elucidated at 2.0 Angstrom resolution. The overall structure of PlGF-1 is similar to that of vascular endothelial growth factor (VEGF) with which it shares 42% amino a cid sequence identity. Based on structural and biochemical data, we have ma pped several important residues on the PlGF-1 molecule that are involved in recognition of the fms-like tyrosine kinase receptor (Flt-1, also known as VEGFR-1). We propose a model for the association of PlGF-1 and Flt-1 domai n 2 with precise shape complementarity, consider the relevance of this asse mbly for PlGF-1 signal transduction, and provide a structural basis for alt ered specificity of this molecule.