Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity

Shalini Iyer, Paula I Darley, K Ravi Acharya

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 angstrom 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.
Original languageEnglish
Pages (from-to)23779-23789
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number31
DOIs
Publication statusPublished - 30 Jul 2010

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Vascular Endothelial Growth Factor B
Vascular Endothelial Growth Factor Receptor-1
Blood vessels
Vascular Endothelial Growth Factor A
Molecules
Blood Vessels
Intercellular Signaling Peptides and Proteins
Physiological Phenomena
Ligands
Tissue regeneration
Angiogenesis Inducing Agents
Receptor Protein-Tyrosine Kinases
Pathology
Wound Healing
Reproduction
Tumors
Regeneration
Crystal structure
Binding Sites
Inflammation

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Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity. / Iyer, Shalini; Darley, Paula I; Acharya, K Ravi.

In: Journal of Biological Chemistry, Vol. 285, No. 31, 30.07.2010, p. 23779-23789.

Research output: Contribution to journalArticle

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