7P5U

Neuropilin-b1 in a complex with a VEGFB-derived peptide

This is a non-PDB format compatible entry.

Summary for 7P5U

• Entry DOI: 10.2210/pdb7p5u/pdb
• Descriptor: Neuropilin-1, MGC0122 (3 entities in total)
• Functional Keywords: neuropilin, vegfb, complex, peptide-lipidation, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 38922.00

Authors

Fotinou, C.,Rhana, R.,Yelland, T. (deposition date: 2021-07-14, release date: 2022-07-27, Last modification date: 2026-03-25)

Primary citation

Mota, F.,Yelland, T.,Hutton, J.A.,Parker, J.,Patsiarika, A.,Chan, A.W.E.,O'Leary, A.,Fotinou, C.,Martin, J.F.,Zachary, I.C.,Djordjevic, S.,Frankel, P.,Selwood, D.L.
Peptides Derived from Vascular Endothelial Growth Factor B Show Potent Binding to Neuropilin-1.
Chembiochem, 23:e202100463-e202100463, 2022

PubMed Abstract: Vascular endothelial growth factors (VEGFs) regulate significant pathways in angiogenesis, myocardial and neuronal protection, metabolism, and cancer progression. The VEGF-B growth factor is involved in cell survival, anti-apoptotic and antioxidant mechanisms, through binding to VEGF receptor 1 and neuropilin-1 (NRP1). We employed surface plasmon resonance technology and X-ray crystallography to analyse the molecular basis of the interaction between VEGF-B and the b1 domain of NRP1, and developed VEGF-B C-terminus derived peptides to be used as chemical tools for studying VEGF-B - NRP1 related pathways. Peptide lipidation was used as a means to stabilise the peptides. VEGF-B-derived peptides containing a C-terminal arginine show potent binding to NRP1-b1. Peptide lipidation increased binding residence time and improved plasma stability. A crystal structure of a peptide with NRP1 demonstrated that VEGF-B peptides bind at the canonical C-terminal arginine binding site. VEGF-B C-terminus imparts higher affinity for NRP1 than the corresponding VEGF-A region. This tight binding may impact on the activity and selectivity of the full-length protein. The VEGF-B derived peptides were more effective than VEGF-A peptides in blocking functional phosphorylation events. Blockers of VEGF-B function have potential applications in diabetes and non-alcoholic fatty liver disease.

PubMed: 34647407
DOI: 10.1002/cbic.202100463

Experimental method

X-RAY DIFFRACTION (1.6 Å)