PDBsum entry: 1fq9

Growth factor/growth factor receptor

PDB id: 1fq9

Contents

Protein chains

129 a.a. *

211 a.a. *

196 a.a. *

Ligands

UAP-SGN-IDS-SGN-IDS-SGN-IDU-SGN

UAP-SGN-IDS-SGN-IDS-SGN

* Residue conservation analysis

PDB id:

1fq9

Name:

Growth factor/growth factor receptor

Title:

Crystal structure of a ternary fgf2-fgfr1-heparin complex

Structure:

Fibroblast growth factor 2. Chain: a, b. Fragment: the b-trefoil core of fibroblast growth factor 2 synonym: fgf2. Engineered: yes. Mutation: yes. Fibroblast growth factor receptor 1. Chain: c, d. Fragment: extracellular ligand binding domain of fgf recept

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:

3.00Å R-factor: 0.229 R-free: 0.282

Authors:

J.Schlessinger,A.N.Plotnikov,O.A.Ibrahimi,A.V.Eliseenkova,B. A.Yayon,R.J.Linhardt,M.Mohammadi

Key ref:

J.Schlessinger et al. (2000). Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol Cell, 6, 743-750. PubMed id: 11030354 DOI: 10.1016/S1097-2765(00)00073-3

Date:

04-Sep-00 Release date: 27-Sep-00

Protein chains

P09038  (FGF2_HUMAN) -  Heparin-binding growth factor 2

Seq: 288 a.a.

Struc: 129 a.a.*

Protein chain

P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1

Seq: 822 a.a.

Struc: 211 a.a.*

Protein chain

P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1

Seq: 822 a.a.

Struc: 196 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains C, D: E.C.2.7.10.1 - Receptor protein-tyrosine kinase.
• Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

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

 Gene Ontology (GO) functional annotation 

• Biochemical function: protein binding (2 terms)

reference

DOI no: 10.1016/S1097-2765(00)00073-3

Mol Cell 6:743-750 (2000)

PubMed id: 11030354

Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization.

J.Schlessinger, A.N.Plotnikov, O.A.Ibrahimi, A.V.Eliseenkova, B.K.Yeh, A.Yayon, R.J.Linhardt, M.Mohammadi.

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.

Selected figure(s)

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.

Figures were selected by the author.