Crotalid venom vascular endothelial growth factors has preferential affinity for VEGFR-1. Characterization of Protobothrops mucrosquamatus venom VEGF.
Pm-VEGF, a novel member ofVEGF family from the venom gland of Taiwan habu (Protobothrops mucrosquamatu), is a disulfide-linked homodimer with 119 amino acid residues. Recombinant fusion Pm-VEGF was expressed in Escherichia coli, purified and refolded. Surface plasmon resonance was used to determine its binding kinetics toVEGF-receptors (VEGFR). Relative to human VEGF165, the binding affinity of Pm-VEGF to the VEGFR-1 was 1.7-fold higher while affinity to the VEGFR-2 was 17-fold lower. But it did not bind the VEGFR-3 or neuropilin-1. Pm-VEGF promoted the proliferation and tissue factor production of endothelial cells, the neovascularization in the chicken chorioallantoic membrane, and increased vascular permeability. It also stimulated tissue-factor production and human monocyte chemotaxis, in accord with its specificity for VEGFR-1. Structural comparison among VEGF-proteins from various viper venoms revealed that the two subfamilies of vipers (Crotalinae and Viperinae) have evolved with distinct receptor-specificities for VEGFR-1 and VEGFR-2, respectively. Discussion on structure-activity relationships of the VEGFs further provided insight into residues important for the receptor-binding and specificities.
Chen
Yuh-Ling
YL
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, Republic of China.
Tsai
Inn-Ho
IH
Hong
Tse-Ming
TM
Tsai
Shu-Huei
SH
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011485:Protein Binding; D016415:Sequence Alignment; D020349:Surface Plasmon Resonance; D013925:Thromboplastin / Q000187:drug effects; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D003435:Crotalid Venoms; D042461:Vascular Endothelial Growth Factor A; D013925:Thromboplastin; D040281:Vascular Endothelial Growth Factor Receptor-1