2XAC

Structural Insights into the Binding of VEGF-B by VEGFR-1D2: Recognition and Specificity

Summary for 2XAC

• Entry DOI: 10.2210/pdb2xac/pdb
• Related: 1FLT 1QSV 1QSZ 1QTY 1RV6 2C7W 2VWE
• Descriptor: VASCULAR ENDOTHELIAL GROWTH FACTOR B, VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 1, GLYCEROL, ... (4 entities in total)
• Functional Keywords: transferase-signaling protein complex, angiogenesis, cysteine-knot protein, mitogen, transferase, signaling protein, transferase/signaling protein
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P49765; Isoform Flt1: Cell membrane; Single-pass type I membrane protein. Isoform sFlt1: Secreted: P17948
• Total number of polymer chains: 4
• Total formula weight: 44826.06

Authors

Iyer, S.,Darley, P.,Acharya, K.R. (deposition date: 2010-03-30, release date: 2010-05-19, Last modification date: 2024-11-20)

Primary citation

Iyer, S.,Darley, P.,Acharya, K.R.
Structural Insights Into the Binding of Vegf-B by Vegfr-1D2: Recognition and Specificity
J.Biol.Chem., 285:23779-, 2010

PubMed Abstract: 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.

PubMed: 20501651
DOI: 10.1074/JBC.M110.130658

Experimental method

X-RAY DIFFRACTION (2.71 Å)