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PDBsum entry 1qsz
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Hormone/growth factor receptor
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PDB id
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1qsz
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of the vegf-Binding domain of flt-1: comparison of its free and bound states.
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Authors
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M.A.Starovasnik,
H.W.Christinger,
C.Wiesmann,
M.A.Champe,
A.M.De vos,
N.J.Skelton.
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Ref.
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J Mol Biol, 1999,
293,
531-544.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.).
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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).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
293,
531-544)
copyright 1999.
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