The Crystal Structure of Human Placenta Growth Factor-1 (PlGF-1), an Angiogenic Protein, at 2.0 Å Resolution

Abstract

The angiogenic molecule placenta growth factor (PIGF) is a member of the cysteine-knot family of growth factors. In this study, a mature isoform of the human PIGF protein, PIGF-1, was crystallized as a homodimer in the crystallographic asymmetric unit, and its crystal structure was elucidated at 2.0 Å resolution. The overall structure of PIGF-1 is similar to that of vascular endothelial growth factor (VEGF) with which it shares 42% amino acid sequence identity. Based on structural and biochemical data, we have mapped several important residues on the PIGF-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 PIGF-1 and Flt-1 domain 2 with precise shape complementarity, consider the relevance of this assembly for PIGF-1 signal transduction, and provide a structural basis for altered specificity of this molecule.