Summary
PDB 2XAC deposited: 2010-03-30 modified: 2010-08-04
Title STRUCTURAL INSIGHTS INTO THE BINDING OF VEGF-B BY VEGFR-1D2: RECOGNITION AND SPECIFICITY
Authors Acharya, K.R., Darley, P., Iyer, S.
Method X-RAY DIFFRACTION
Structure factors resolution 2.71 rfactor 0.282 rfree 0.364
DPI 1.30 theoretical min: 0.62
Citations

The formation of blood vessels (angiogenesis) is a highly orchestrated sequence of events involving crucial receptor-ligand interactions. Angiogenesis is critical for physiological processes such as development, wound healing, reproduction, tissue regeneration, and remodeling. It also plays a major role in sustaining tumor progression and chronic inflammation. Vascular endothelial growth factor (VEGF)-B, a member of the VEGF family of angiogenic growth factors, effects blood vessel formation by binding to a tyrosine kinase receptor, VEGFR-1. There is growing evidence of the important role played by VEGF-B in physiological and pathological vasculogenesis. Development of VEGF-B antagonists, which inhibit the interaction of this molecule with its cognate receptor, would be important for the treatment of pathologies associated specifically with this growth factor. In this study, we present the crystal structure of the complex of VEGF-B with domain 2 of VEGFR-1 at 2.7 A resolution. Our analysis reveals that each molecule of the ligand engages two receptor molecules using two symmetrical binding sites. Based on these interactions, we identify the receptor-binding determinants on VEGF-B and shed light on the differences in specificity towards VEGFR-1 among the different VEGF homologs.

J.Biol.Chem. 2010 Jul; 285(31):23779-23789 doi:10.1074/jbc.M110.130658

Cross References
Database source Identifier Description
PubMed 20501651 JBCHA3
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2XAC/1 2XAC 1 tetramer 0 4 1 2894