Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A

15Citations
Citations of this article
62Readers
Mendeley users who have this article in their library.

Abstract

Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel development upon activation of three receptor tyrosine kinases: VEGFR-1, -2, and -3. Partial structures of VEGFR/VEGF complexes based on single-particle electron microscopy, small-angle X-ray scattering, and X-ray crystallography revealed the location of VEGF binding and domain arrangement of individual receptor subdomains. Here, we describe the structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A at 4 Å resolution. We combined X-ray crystallography, single-particle electron microscopy, and molecular modeling for structure determination and validation. The structure reveals the molecular details of ligand-induced receptor dimerization, in particular of homotypic receptor interactions in immunoglobulin homology domains 4, 5, and 7. Functional analyses of ligand binding and receptor activation confirm the relevance of these homotypic contacts and identify them as potential therapeutic sites to allosterically inhibit VEGFR-1 activity.

Cite

CITATION STYLE

APA

Markovic-Mueller, S., Stuttfeld, E., Asthana, M., Weinert, T., Bliven, S., Goldie, K. N., … Ballmer-Hofer, K. (2017). Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A. Structure, 25(2), 341–352. https://doi.org/10.1016/j.str.2016.12.012

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free