1QSZ

THE VEGF-BINDING DOMAIN OF FLT-1 (MINIMIZED MEAN)

Summary for 1QSZ

• Entry DOI: 10.2210/pdb1qsz/pdb
• Related: 1FLT 1QSV
• Descriptor: VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 1 (1 entity in total)
• Functional Keywords: immunoglobulin-like domain, i-set, vegf receptor, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Flt1: Cell membrane; Single-pass type I membrane protein. Isoform sFlt1: Secreted: P17948
• Total number of polymer chains: 1
• Total formula weight: 11538.30

Authors

Starovasnik, M.A.,Christinger, H.W.,Wiesmann, C.,Champe, M.A.,de Vos, A.M.,Skelton, N.J. (deposition date: 1999-06-24, release date: 1999-11-10, Last modification date: 2024-10-30)

Primary citation

Starovasnik, M.A.,Christinger, H.W.,Wiesmann, C.,Champe, M.A.,de Vos, A.M.,Skelton, N.J.
Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states.
J.Mol.Biol., 293:531-544, 1999

PubMed Abstract: 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.

PubMed: 10543948
DOI: 10.1006/jmbi.1999.3134

Experimental method

SOLUTION NMR