Platelet-derived growth factor (PDGF)-C, a PDGF family member with a vascular endothelial growth factor-like structure
Platelet-derived growth factor (PDGF)-C, a PDGF family member with a vascular endothelial growth factor-like structure
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DOI：
10.1074/jbc.m301728200
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发表时间：
2003-05-09
影响因子：
4.8
通讯作者：
Lillehaug, JR
中科院分区：
文献类型：
--
作者：
Reigstad, LJ;Sande, HM;Lillehaug, JR
血小板源性生长因子（血小板衍生生长因子）-C是血小板衍生生长因子家族的新成员，可与血小板衍生生长因子α和α受体结合。在大肠杆菌中高效表达了PDGF-C的生长因子结构域（GFD-PDGF-C），并从包涵体中纯化和复性，获得了具有生物活性的二聚体生长因子。GFD-PDGF-C含有12个半胱氨酸残基，Ellman测定分析表明其含有三个单体内二硫键，这与GFD-PDGF-C是生长因子的胱氨酸结超家族的成员一致。重组GFD-PDGF-C通过CD、荧光、NMR和红外光谱进行表征。总之，我们的数据表明，GFD-PDGF-C是一种高度热稳定的蛋白质，主要含有β折叠二级结构和一些（6%）α螺旋结构。使用该生长因子家族的结构代表通过基于同源性的分子建模获得的PDGF-C的结构模型表明，GFD-PDGF-C与血管内皮生长因子的结构同源性高于与PDGF-B的结构同源性。模型化的结构可以进一步了解这种分子的功能和特异性。
Platelet-derived growth factor (PDGF)-C is a novel member of the PDGF family that binds to PDGF alphaalpha and alphabeta receptors. The growth factor domain of PDGF-C (GFD-PDGF-C) was expressed in high yields in Escherichia coli and was purified and refolded from inclusion bodies obtaining a biologically active growth factor with dimeric structure. The GFD-PDGF-C contains 12 cysteine residues, and Ellman assay analysis indicates that it contains three intramonomeric disulfide bonds, which is in accordance with GFD-PDGF-C being a member of the cystine knot superfamily of growth factors. The recombinant GFD-PDGF-C was characterized by CD, fluorescence, NMR, and infrared spectroscopy. Together, our data indicate that GFD-PDGF-C is a highly thermostable protein that contains mostly beta-sheet secondary structure and some (6%) alpha-helix structure. The structural model of PDGF-C, obtained by homology-based molecular modeling using the structural representatives of this family of growth factors, shows that GFD-PDGF-C has a higher structural homology to the vascular endothelial growth factor than to PDGF-B. The modeled structure can give further insights into the function and specificity of this molecule.