@article {45,
	title = {Structural determinants of vascular endothelial growth factor-D receptor binding and specificity},
	journal = {Blood},
	volume = {117},
	year = {2011},
	month = {2011/Feb/},
	pages = {1507 - 15},
	abstract = {Vascular endothelial growth factors (VEGFs) and their tyrosine kinase receptors (VEGFR-1-3) are central mediators of angiogenesis and lymphangiogenesis. VEGFR-3 ligands VEGF-C and VEGF-D are produced as precursor proteins with long N- and C-terminal propeptides and show enhanced VEGFR-2 and VEGFR-3 binding on proteolytic removal of the propeptides. Two different proteolytic cleavage sites have been reported in the VEGF-D N-terminus. We report here the crystal structure of the human VEGF-D Cys117Ala mutant at 2.9 {\r A} resolution. Comparison of the VEGF-D and VEGF-C structures shows similar extended N-terminal helices, conserved overall folds, and VEGFR-2 interacting residues. Consistent with this, the affinity and the thermodynamic parameters for VEGFR-2 binding are very similar. In comparison with VEGF-C structures, however, the VEGF-D N-terminal helix was extended by 2 more turns because of a better resolution. Both receptor binding and functional assays of N-terminally truncated VEGF-D polypeptides indicated that the residues between the reported proteolytic cleavage sites are important for VEGF-D binding and activation of VEGFR-3, but not of VEGFR-2. Thus, we define here a VEGFR-2-specific form of VEGF-D that is angiogenic but not lymphangiogenic. These results provide important new insights into VEGF-D structure and function.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/21148085},
	author = {Lepp{\"a}nen, Veli-Matti and Jeltsch, Michael and Anisimov, Andrey and Tvorogov, Denis and Aho, Kukka and Kalkkinen, Nisse and Toivanen, Pyry and Yl{\"a}-Herttuala, Seppo and Ballmer-Hofer, Kurt and Alitalo, Kari}
}
