Structural basis for the interaction of a vascular endothelial growth factor mimic peptide motif and its corresponding receptors |
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Authors: | Giordano Ricardo J Anobom Cristiane D Cardó-Vila Marina Kalil Jorge Valente Ana P Pasqualini Renata Almeida Fabio C L Arap Wadih |
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Institution: | The University of Texas, MD Anderson Cancer Center, Houston, 77030, USA. |
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Abstract: | Vascular endothelial growth factor (VEGF) is central to the survival and development of the vascular and nervous systems. We screened phage display libraries and built a peptide-based ligand-receptor map of binding sites within the VEGF family. We then validated a cyclic peptide, CPQPRPLC, as a VEGF-mimic that binds specifically to neuropilin-1 and VEGF receptor-1. Here, we use NMR spectroscopy to understand the structural basis of the interaction between our mimic peptide and the VEGF receptors. We show that: (1) CPQPRPLC has multiple interactive conformations; (2) receptor binding is mediated by the motif Arg-Pro-Leu; and (3) the Pro residue within Arg-Pro-Leu participates in binding to neuropilin-1 but not to VEGF receptor-1, perhaps representing an evolutionary gain-of-function. Therefore, Arg-Pro-Leu is a differential ligand motif to VEGF receptors and a candidate peptidomimetic lead for VEGF pathway modulation. |
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