Summary
PDB 1QTY deposited: 1999-06-29 modified: 2009-02-24
Title VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR
Authors Champe, M.A., Christinger, H.W., de Vos, A.M., Skelton, N.J., Starovasnik, M.A., Wiesmann, C.
Method X-RAY DIFFRACTION
Structure factors resolution 2.7 rfactor 0.2327 rfree 0.2844
DPI 1.12 theoretical min: 0.48
Related PDB Entries 1QSV 1QSZ
Citations

The extracellular portion of the VEGF and PlGF receptor, Flt-1 (or VEGFR-1), consists of seven immunoglobulin-like domains. The second domain from the N terminus (Flt-1D2) is necessary and sufficient for high affinity VEGF binding. The 1.7 A resolution crystal structure of Flt-1D2 bound to VEGF revealed that this domain is a member of the I-set of the immunoglobulin superfamily, but has several unusual features including a region near the N terminus that bulges away from the domain rather than pairing with the neighboring beta-strand. Some of the residues in this region make contact with VEGF, raising the possibility that this bulge could be a consequence of VEGF binding and might not be present in the absence of ligand. Here we report the three-dimensional structure of Flt-1D2 in its uncomplexed form determined by NMR spectroscopy. A semi-automated method for NOE assignment that takes advantage of the previously solved crystal structure was used to facilitate rapid analysis of the 3D NOESY spectra. The solution structure is very similar to the previously reported VEGF-bound crystal structure; the N-terminal bulge is present, albeit in a different conformation. We also report the 2.7 A crystal structure of Flt-1D2 in complex with VEGF solved in a different crystal form that reveals yet another conformation for the N-terminal bulge region. (1)H-(15)N heteronuclear NOEs indicate this region is flexible in solution; the crystal structures show that this region is able to adopt more than one conformation even when bound to VEGF. Thus, VEGF-binding is not accompanied by significant structural change in Flt-1D2, and the unusual structural features of Flt-1D2 are an intrinsic property of this domain.

J.Mol.Biol. 1999 Oct; 293(3):531-544 doi:10.1006/jmbi.1999.3134

Cross References
Database source Identifier Description
PubMed 10543948 JMOBAK
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1QTY/1 1QTY 1 tetramer 0 4 0 2902
1QTY/2 1QTY 2 tetramer 0 4 0 2909
1QTY/3 1QTY 3 octamer 0 8 0 5811