PDBsum entry 1qty

Hormone/growth factor receptor

PDB id: 1qty

Contents

Protein chains

95 a.a. *

94 a.a. *

* Residue conservation analysis

PDB id:

1qty

Name:

Hormone/growth factor receptor

Title:

Vascular endothelial growth factor in complex with domain 2 of the flt-1 receptor

Structure:

Vascular endothelial growth factor. Chain: v, w, r, s. Fragment: receptor binding domain. Engineered: yes. Fms-like tyrosine kinase 1. Chain: x, y, t, u. Fragment: domain 2. Synonym: flt-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Biol. unit:

Octamer (from PQS)

Resolution:

2.70Å R-factor: 0.233 R-free: 0.284

Authors:

C.Wiesmann,A.M.De Vos

Key ref:

M.A.Starovasnik et al. (1999). Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states. J Mol Biol, 293, 531-544. PubMed id: 10543948 DOI: 10.1006/jmbi.1999.3134

Date:

29-Jun-99 Release date: 12-Jan-00

Protein chains

P15692  (VEGFA_HUMAN) -  Vascular endothelial growth factor A, long form from Homo sapiens

Seq: 395 a.a.

Struc: 95 a.a.

Protein chains

P17948  (VGFR1_HUMAN) -  Vascular endothelial growth factor receptor 1 from Homo sapiens

Seq: 1338 a.a.

Struc: 94 a.a.

Enzyme reactions

• Enzyme class: Chains X, Y, T, U: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1006/jmbi.1999.3134

J Mol Biol 293:531-544 (1999)

PubMed id: 10543948

Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states.

M.A.Starovasnik, H.W.Christinger, C.Wiesmann, M.A.Champe, A.M.de Vos, N.J.Skelton.

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.

Selected figure(s)

Figure 3.
Figure 3. Solution structure of Flt-1D2. The 20 final structures are shown superposed using backbone atoms of residues in the b-strands (colored red or blue). Strands are labeled as described (Wiesmann et al., 1997); the helical turn is colored green, and the disulfide bond buried in the core of the domain is colored yellow. This Figure and Figures 7-9 were generated using INSIGHT 97.0 (Molecular Simulations, Inc.).

Figure 6.
Figure 6. Ribbon diagram of the 2.7 Å resolution Flt-1D2/VEGF crystal structure. The two copies of Flt-1D2 are shown in blue; the two chains of the covalent VEGF dimer are shown in orange and yellow. (a) Side view, the membrane would be at the bottom in this orientation; (b) top view, 90 ° rotation from (a). This Figure was prepared using the program MOLSCRIPT (Kraulis, 1991).

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 293, 531-544) copyright 1999.

Figures were selected by the author.