9EOU

Crystal Structure of the b1b2 domains from Human Neuropilin-1 in complex with a peptide.

これはPDB形式変換不可エントリーです。

9EOU の概要

• エントリーDOI: 10.2210/pdb9eou/pdb
• 分子名称: Neuropilin-1, Osteopontin (3 entities in total)
• 機能のキーワード: angiogenesis, neuropilin-1, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37734.76

構造登録者

Caing-Carlsson, R.,Duelli, A.,Walse, B. (登録日: 2024-03-15, 公開日: 2024-06-26, 最終更新日: 2024-10-09)

主引用文献

Chen, Y.,Gialeli, C.,Shen, J.,Duner, P.,Walse, B.,Duelli, A.,Caing-Carlsson, R.,Blom, A.M.,Zibert, J.R.,Nilsson, A.H.,Alenfall, J.,Liang, C.,Nilsson, J.
Identification of an osteopontin-derived peptide that binds neuropilin-1 and activates vascular repair responses and angiogenesis.
Pharmacol Res, 205:107259-107259, 2024

PubMed Abstract: The osteopontin-derived peptide FOL-005 stimulates hair growth. Using ligand-receptor glyco-capture technology we identified neuropilin-1 (NRP-1), a known co-receptor for vascular endothelial growth factor (VEGF) receptors, as the most probable receptor for FOL-005 and the more stable analogue FOL-026. X-ray diffraction and microscale thermophoresis analysis revealed that FOL-026 shares binding site with VEGF in the NRP-1 b1-subdomain. Stimulation of human umbilical vein endothelial cells with FOL-026 resulted in phosphorylation of VEGFR-2, ERK1/2 and AKT, increased cell growth and migration, stimulation of endothelial tube formation and inhibition of apoptosis in vitro. FOL-026 also promoted angiogenesis in vivo as assessed by subcutaneous Matrigel plug and hind limb ischemia models. NRP-1 knock-down or treatment of NRP-1 antagonist EG00229 blocked the stimulatory effects of FOL-026 on endothelial cells. Exposure of human coronary artery smooth muscle cells to FOL-026 stimulated cell growth, migration, inhibited apoptosis, and induced VEGF gene expression and VEGFR-2/AKT phosphorylation by an NRP-1-dependent mechanism. RNA sequencing showed that FOL-026 activated pathways involved in tissue repair. These findings identify NRP-1 as the receptor for FOL-026 and show that its biological effects mimic that of growth factors binding to the VEGF receptor family. They also suggest that FOL-026 may have therapeutical potential in conditions that require vascular repair and/or enhanced angiogenesis.

PubMed: 38871237
DOI: 10.1016/j.phrs.2024.107259

実験手法

X-RAY DIFFRACTION (1.55 Å)