PDBsum entry: 1evt

Growth factor/growth factor receptor

PDB-id: 1evt

Biological unit* = asymmetric unit,
as shown
(*as deduced by PQS)

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

131 a.a. *

191 a.a. *

Ligands

SO4 ×4

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

1evt

Name:

Growth factor/growth factor receptor

Title:

Crystal structure of fgf1 in complex with the extracellular ligand binding domain of fgf receptor 1 (fgfr1)

Structure:

Protein (fibroblast growth factor 1). Chain: a, b. Fragment: the b-trefoil core of fibroblast growth factor 1 (fgf1). Synonym: fgf1. Engineered: yes. Protein (fibroblast growth factor receptor 1). Chain: c, d. Fragment: extracellular ligand binding domain of fgf

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: bacteria. Expression_system_taxid: 2. Expression_system_taxid: 2

Biological unit:

Tetramer (from PQS)

UniProt:

Chains A, B: P05230 (FGF1_HUMAN)

Seq:	155 a.a.
Struc:	131 a.a.

Chains C, D: P11362 (FGFR1_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

822 a.a.

Struc:

191 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Enzyme class:

Chains C, D: E.C.2.7.10.1   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

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

Resolution:

2.80Å

R-factor:

0.249

R-free:

0.300

Authors:

A.N.Plotnikov,S.R.Hubbard,J.Schlessinger,M.Mohammadi

Key ref:

A.N.Plotnikov et al. (2000). Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.. Cell, 101, 413-424. [PubMed id: 10830168] [DOI: 10.1016/S0092-8674(00)80851-X]

Date:

20-Apr-00

Release date:

31-May-00

Related entries:

1cvs
crystal structure of fgf2 in complex with the extracellular
ligand binding domain of fgf receptor 1 (fgfr1)
1evt
fgf1-fgfr1 complex

Quick_links

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Surface

Key reference

DOI no: 10.1016/S0092-8674(00)80851-X

Cell 101:413-424 (2000)

PubMed id: 10830168

Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.

A.N.Plotnikov, S.R.Hubbard, J.Schlessinger, M.Mohammadi.

ABSTRACT

To elucidate the structural determinants governing specificity in fibroblast growth factor (FGF) signaling, we have determined the crystal structures of FGF1 and FGF2 complexed with the ligand binding domains (immunoglobulin-like domains 2 [D2] and 3 [D3]) of FGF receptor 1 (FGFR1) and FGFR2, respectively. Highly conserved FGF-D2 and FGF-linker (between D2-D3) interfaces define a general binding site for all FGF-FGFR complexes. Specificity is achieved through interactions between the N-terminal and central regions of FGFs and two loop regions in D3 that are subject to alternative splicing. These structures provide a molecular basis for FGF1 as a universal FGFR ligand and for modulation of FGF-FGFR specificity through primary sequence variations and alternative splicing.

Selected figure(s)

Figure 3.
Figure 3. Detailed Interactions between FGF and FGFR in the FGF-D2 and FGF-Linker Interfaces(A) Stereo view of the hydrophobic interface between FGF2 and D2 of FGFR2.(B) Stereo view of the hydrophobic interface between FGF1 and D2 of FGFR1.(C) Stereo view of the conserved network of hydrogen bonds between FGF2 and FGFR2 in the vicinity of Arg-251 in the D2-D3 linker.(D) Stereo view of the network of hydrogen bonds between FGF1 and FGFR1 in the vicinity of Arg-250 in the D2-D3 linker. Only side chains of interacting residues are shown. At the right side of each stereo pair, a view of the whole structure in the exact orientation as in stereo views is shown, and the region of interest is highlighted. Color coding is the same as in Figure 1: FGF1 and FGF2 in orange, D2 in green, D3 in cyan, and the linker in gray. Oxygen atoms are colored red, nitrogen atoms blue, and carbon atoms have the same coloring as the molecules to which they belong. Dotted lines represent hydrogen bonds. This figure was created using the programs Molscript and Raster3D.

Figure 4.
Figure 4. Detailed Interactions between FGF and FGFR in the FGF-D3 Interfaces(A) Stereo view of the interface between FGF2 and the βF-βG loop of D3 in the FGF2-FGFR2 structure.(B) Stereo view of the interface between N-terminal sequences (prior to β1) of FGF2 and D3 in the FGF2-FGFR2 structure.(C) Stereo view of the interface between FGF2 and the βC′-βE segment (shown in purple) of D3 in the FGF2-FGFR2 structure.(D) Stereo view of the interface between FGF1 and D3 in the FGF1-FGFR1 structure. At the right side of each stereo pair, a view of the whole structure in the exact orientation as in stereo views is shown, and the region of interest is highlighted. Only side chains of interacting residues are shown. Color coding is the same as in Figure 3. Dotted lines represent hydrogen bonds. This figure was created using the programs Molscript and Raster3D.

The above figures are reprinted by permission from Cell Press: Cell (2000, 101, 413-424) copyright 2000.

Figures were selected by the author.