 |
PDBsum entry 1fq9
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Growth factor/growth factor receptor
|
PDB id
|
|
|
|
1fq9
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
129 a.a.
|
|
|
|
|
|
|
|
|
|
|
211 a.a.
|
|
|
|
|
|
|
|
|
|
|
196 a.a.
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of a ternary fgf-Fgfr-Heparin complex reveals a dual role for heparin in fgfr binding and dimerization.
|
|
|
Authors
|
|
J.Schlessinger,
A.N.Plotnikov,
O.A.Ibrahimi,
A.V.Eliseenkova,
B.K.Yeh,
A.Yayon,
R.J.Linhardt,
M.Mohammadi.
|
|
|
Ref.
|
|
Mol Cell, 2000,
6,
743-750.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex at 3 A
resolution has been determined. Within each 1:1 FGF:FGFR complex, heparin makes
numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding.
Heparin also interacts with FGFR in the adjoining 1:1 FGF:FGFR complex to
promote FGFR dimerization. The 6-O-sulfate group of heparin plays a pivotal role
in mediating both interactions. The unexpected stoichiometry of heparin binding
in the structure led us to propose a revised model for FGFR dimerization.
Biochemical data in support of this model are also presented. This model
provides a structural basis for FGFR activation by small molecule heparin
analogs and may facilitate the design of heparin mimetics capable of modulating
FGF signaling.
|
|
|
|
|
|
|
|
Figure 1.
Figure 1. Electron Density Map of Decasaccharides Soaked
into Preformed Crystals of an FGF2-FGFR1 Complex(A) Location of
decasaccharides in the dimeric assemblage. Only the C[α] traces
of D2s (cyan) and FGFs (orange) are shown. The decasaccharides
are rendered in white sticks.(B) Stereo view of F[o] −F[c]
electron density map computed after simulated annealing with
decasaccharide omitted from the atomic model. The map is
computed at 3.0 Å resolution and contoured at 1.8 σ.
Sugar rings are labeled A through H starting at the nonreducing
end of the decasaccharide. Atom coloring is as follows: oxygens
in red, sulfurs in yellow, nitrogens in blue, and carbons in
gray. This figure was made using Bobscript ([4]).
|
|
Figure 4.
Figure 4. The Two-End ModelMolecular surface representation
of the dimeric 2:2:2 FGF2-FGFR1-heparin ternary complex. The
view is from the top (same view as Figure 1A ) looking down into
the heparin binding canyon. Surface coloring is as follows: FGF2
in orange and D2 in green. Only the first six sugar rings of the
decasaccharides are rendered in ball-and-stick, and the
nonreducing and reducing ends are labeled. This figure was
created with GRASP ( [20]).
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2000,
6,
743-750)
copyright 2000.
|
|
|
|
|
|
|
