PDBsum entry: 1cvs

Growth factor/growth factor receptor

PDB-id: 1cvs

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

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Description

Header details

Header records

References

PROCHECK

Protein chains

129 a.a. *

211 a.a. *

196 a.a. *

Ligands

SO4 ×4

* Residue conservation analysis

Tools

Clefts Calculation

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PDB id:

1cvs

Name:

Growth factor/growth factor receptor

Title:

Crystal structure of a dimeric fgf2-fgfr1 complex

Structure:

Fibroblast growth factor 2. Chain: a, b. Engineered: yes. Mutation: yes. Fibroblast growth factor receptor 1. Chain: c, d. Fragment: ig-like domains 2 and 3. Engineered: yes. Mutation: yes

Source:

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

Biological unit:

Tetramer (from PQS)

UniProt:

Chains A, B: P09038 (FGF2_HUMAN)

Seq:	210 a.a.
Struc:	129 a.a.*

Chain C: P11362 (FGFR1_HUMAN)

Seq:
Struc:
	Seq:
	Struc:
Seq:
Struc:
	Seq:	822 a.a.
	Struc:	211 a.a.*

Chain D: P11362 (FGFR1_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

822 a.a.

Struc:

196 a.a.*

Key:	PfamA domain
Secondary structure	CATH domain

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

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:

0.240

R-free:

0.281

Authors:

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

Key ref:

A.N.Plotnikov et al. (1999). Structural basis for FGF receptor dimerization and activation.. Cell, 98, 641-650. [PubMed id: 10490103] [DOI: 10.1016/S0092-8674(00)80051-3]

Date:

24-Aug-99

Release date:

28-Jan-00

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Key reference

DOI no: 10.1016/S0092-8674(00)80051-3

Cell 98:641-650 (1999)

PubMed id: 10490103

Structural basis for FGF receptor dimerization and activation.

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

ABSTRACT

The crystal structure of FGF2 bound to a naturally occurring variant of FGF receptor 1 (FGFR1) consisting of immunoglobulin-like domains 2 (D2) and 3 (D3) has been determined at 2.8 A resolution. Two FGF2:FGFR1 complexes form a 2-fold symmetric dimer. Within each complex, FGF2 interacts extensively with D2 and D3 as well as with the linker between the two domains. The dimer is stabilized by interactions between FGF2 and D2 of the adjoining complex and by a direct interaction between D2 of each receptor. A positively charged canyon formed by a cluster of exposed basic residues likely represents the heparin-binding site. A general model for FGF- and heparin-induced FGFR dimerization is inferred from the crystal structure, unifying a wealth of biochemical data.

Selected figure(s)

Figure 4.
Figure 4. Mapping of the Different Interaction Sites onto the Molecular Surfaces of FGF2 and FGFR1The surface color codings for D2, D3, the linker, and FGF2 are the same as in Figure 1. The surfaces of FGF2 and FGFR1 that form the primary and secondary interaction sites are shown in red and purple, respectively. The heparin-binding surfaces are depicted in blue. The surface on D2 engaged in direct receptor–receptor interaction is colored yellow. To better visualize the different functional surfaces on FGF2 and D23, the two molecules are pulled away from each other and rotated 90° about the vertical axis. This figure was created using the program GRASP ( [33]).

Figure 5.
Figure 5. The Primary Interaction Site between FGF2 and FGFR1(A) Stereo view of the hydrophobic interface between FGF2 and D2 of FGFR1. Only side chains of interacting residues are shown. Color coding is the same as in Figure 1: FGF2 in orange, D2 in green, D3 in blue, and the linker in gray. Dotted lines represent hydrogen bonds.(B) Stereo view of the network of hydrogen bonds between FGF2 and FGFR1 in the vicinity of Arg-250 in the D2–D3 linker.(C) Stereo view of the interface between FGF2 and D3 of FGFR1. This figure was created using the programs Molscript and Raster3D.

The above figures are reprinted by permission from Cell Press: Cell (1999, 98, 641-650) copyright 1999.

Figures were selected by an automated process.