Platelet-derived growth factor (PDGF)-C, a PDGF family member with a vascular endothelial growth factor-like structure.
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.
Reigstad
Laila J
LJ
Department of Molecular Biology, University of Bergen, Bergen 5009, Norway.
Sande
Hege M
HM
Fluge
Øystein
Ø
Bruland
Ove
O
Muga
Arturo
A
Varhaug
Jan Erik
JE
Martinez
Aurora
A
Lillehaug
Johan R
JR
D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D002942:Circular Dichroism; D006801:Humans; D008222:Lymphokines; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A
D043925:Angiogenesis Inducing Agents; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C411423:platelet-derived growth factor C