Iyer S, Leonidas D D, Swaminathan G J, Maglione D, Battisti M, Tucci M, Persico M G, Acharya K R
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
J Biol Chem. 2001 Apr 13;276(15):12153-61. doi: 10.1074/jbc.M008055200. Epub 2000 Nov 7.
The angiogenic molecule placenta growth factor (PlGF) is a member of the cysteine-knot family of growth factors. In this study, a mature isoform of the human PlGF protein, PlGF-1, was crystallized as a homodimer in the crystallographic asymmetric unit, and its crystal structure was elucidated at 2.0 A resolution. The overall structure of PlGF-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 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 domain 2 with precise shape complementarity, consider the relevance of this assembly for PlGF-1 signal transduction, and provide a structural basis for altered specificity of this molecule.
血管生成分子胎盘生长因子（PlGF）是生长因子的半胱氨酸结家族成员。在本研究中，人PlGF蛋白的成熟异构体PlGF-1在晶体学不对称单元中结晶为同二聚体，并在2.0埃分辨率下解析了其晶体结构。PlGF-1的整体结构与血管内皮生长因子（VEGF）相似，二者氨基酸序列一致性为42%。基于结构和生化数据，我们在PlGF-1分子上定位了几个与类fms酪氨酸激酶受体（Flt-1，也称为VEGFR-1）识别有关的重要残基。我们提出了一个PlGF-1与Flt-1结构域2精确形状互补结合的模型，考虑了该组装对PlGF-1信号转导的相关性，并为该分子特异性改变提供了结构基础。
