1qsv
From Proteopedia
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THE VEGF-BINDING DOMAIN OF FLT-1, 20 NMR STRUCTURES
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Fanconi renotubular syndrome OMIM:[134600], Jackson-Weiss syndrome OMIM:[136350], Kallmann syndrome 2 OMIM:[136350], Pfeiffer syndrome OMIM:[136350]
About this Structure
1QSV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states., Starovasnik MA, Christinger HW, Wiesmann C, Champe MA, de Vos AM, Skelton NJ, J Mol Biol. 1999 Oct 29;293(3):531-44. PMID:10543948
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