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PDBsum entry 1djs
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Hormone/growth factor/receptor
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PDB id
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1djs
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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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Structural interactions of fibroblast growth factor receptor with its ligands.
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Authors
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D.J.Stauber,
A.D.Digabriele,
W.A.Hendrickson.
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Ref.
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Proc Natl Acad Sci U S A, 2000,
97,
49-54.
[DOI no: ]
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PubMed id
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Abstract
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Fibroblast growth factors (FGFs) effect cellular responses by binding to FGF
receptors (FGFRs). FGF bound to extracellular domains on the FGFR in the
presence of heparin activates the cytoplasmic receptor tyrosine kinase through
autophosphorylation. We have crystallized a complex between human FGF1 and a
two-domain extracellular fragment of human FGFR2. The crystal structure,
determined by multiwavelength anomalous diffraction analysis of the
selenomethionyl protein, is a dimeric assemblage of 1:1 ligand:receptor
complexes. FGF is bound at the junction between the two domains of one FGFR, and
two such units are associated through receptor:receptor and secondary
ligand:receptor interfaces. Sulfate ion positions appear to mark the course of
heparin binding between FGF molecules through a basic region on receptor D2
domains. This dimeric assemblage provides a structural mechanism for FGF signal
transduction.
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Figure 3.
Fig. 3. Dimeric assemblage. (A) Stereoview of a worm
diagram oriented with the diad axis vertical and viewed with the
two FGF1:FGFR2 complexes at either side. FGF1 chains are in red,
the ipsilateral receptor chain (as rotated   40°
from Fig. 1) is in blue, and the contralateral chain is in
green. Receptor segments in ligand contacts are in yellow. (B)
Close-up of a primary D2 contact viewed at 70° from A. (C)
Close-up of a D3 contact viewed at 40° from A. Drawings were
made by GRASP (37).
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Figure 4.
Fig. 4. Heparin binding site. A-C have the dimeric
assemblage oriented as viewed from above Fig. 3A; B-D use the
same color codes as in Fig. 3. (A) Electrostatic potential
surface. Potential is graded from red ( ) to deep
blue (>+16 kT). (B) Sulfate sites superimposed on the molecular
surface. Sulfate ions in the surface channel of the complex are
shown in yellow and sulfonate ions transformed from the
FGF1:heparin structure (8) are in orange. (C) Heparin model
(yellow) superimposed onto worm diagram. Six hexoses at each end
are transformed directly from Ref. 8, and four in the middle are
model built. Side chains of basic residues 176, 178, 208, and
210 are in purple. (D) End view of heparin superimposed onto
worm. The view is rotated by 20°
from Fig. 3A. Drawings were made by GRASP (37).
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