PDBsum entry: 1djs

Hormone/growth factor/receptor

PDB-id: 1djs

Asymmetric unit

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

206 a.a. *

135 a.a. *

Ligands

SO4 ×9

Waters ×319

* Residue conservation analysis

Tools

Clefts Calculation

Biological unit, octamer
- as defined in PDB file (see also PQS)

PDB id:

1djs

Name:

Hormone/growth factor/receptor

Title:

Ligand-binding portion of fibroblast growth factor receptor 2 in complex with fgf1

Structure:

Protein (fibroblast growth factor receptor 2). Chain: a. Fragment: ig-like domains 2 and 3. Engineered: yes. Mutation: yes. Protein (fibroblast growth factor 1). Chain: b. Engineered: yes

Source:

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

Biological unit:

Octamer (from PDB file)

UniProt:

Chain A: P21802 (FGFR2_HUMAN)

Seq:
Struc:
	Seq:
	Struc:
Seq:
Struc:
	Seq:	821 a.a.
	Struc:	206 a.a.*

Chain B: P05230 (FGF1_HUMAN)

Seq:

155 a.a.

Struc:

135 a.a.

Key:	PfamA domain	PfamB domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme class:

Chain A: E.C.2.7.10.1   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

Resolution:

2.40Å

R-factor:

0.227

R-free:

0.315

Authors:

D.J.Stauber,A.D.Digabriele,W.A.Hendrickson

Key ref:

D.J.Stauber et al. (2000). Structural interactions of fibroblast growth factor receptor with its ligands.. Proc Natl Acad Sci U S A, 97, 49-54. [PubMed id: 10618369] [DOI: 10.1073/pnas.97.1.49]

Date:

03-Dec-99

Release date:

12-Jan-00

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1073/pnas.97.1.49

Proc Natl Acad Sci U S A 97:49-54 (2000)

PubMed id: 10618369

Structural interactions of fibroblast growth factor receptor with its ligands.

D.J.Stauber, A.D.DiGabriele, W.A.Hendrickson.

ABSTRACT

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.

Selected figure(s)

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).

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).

Figures were selected by the author.