9IVT
Crystal structure of Ang1 receptor-binding domain
Summary for 9IVT
| Entry DOI | 10.2210/pdb9ivt/pdb |
| Descriptor | Angiopoietin-1 (2 entities in total) |
| Functional Keywords | angiopoietin-1, cell adhesion |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 26188.31 |
| Authors | |
| Primary citation | Wang, R.,Li, H.,Xie, Z.,Huang, M.,Xu, P.,Yuan, C.,Li, J.,Flaumenhaft, R.,Huang, M.,Jiang, L. Development of a recombinant Ang1 variant with enhanced Tie2 binding and its application to attenuate sepsis in mice. Sci Adv, 11:eads1796-eads1796, 2025 Cited by PubMed Abstract: The angiopoietin (Ang)-Tie axis, critical for endothelial cell function and vascular development, is a promising therapeutic target for treating vascular disorders and inflammatory conditions like sepsis. This study aimed to enhance the binding affinity of recombinant Ang1 variants to the Tie2 and explore their therapeutic potential. Structural insights from the Ang1-Tie2 complex enabled the identification of key residues within the Ang1 receptor binding domain (RBD) critical for Tie2 interaction. Molecular dynamics simulations revealed that MetArg (M436R) and AlaAsp (A451D) could improve Ang1's Tie2 binding affinity. One variant, Ang1-RBD, demonstrated a 100-fold increase compared to the wild type. Cellular assays revealed that Ang1 enhanced Tie2 phosphorylation, promoting endothelial cell migration and tube formation. In vivo, this variant effectively reduced inflammatory cytokines and attenuated organ damage in septic mice. These findings highlight Ang1 as a promising therapeutic candidate for vascular diseases, offering notable clinical potential for mitigating sepsis-related vascular dysfunction. PubMed: 39813336DOI: 10.1126/sciadv.ads1796 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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