PDBsum entry: 1ihk

Hormone/growth factor

PDB id: 1ihk

Contents

Protein chain

157 a.a. *

Ligands

PO4 ×2

Waters ×68

* Residue conservation analysis

PDB id:

1ihk

Name:

Hormone/growth factor

Title:

Crystal structure of fibroblast growth factor 9 (fgf9)

Structure:

Glia-activating factor. Chain: a. Fragment: residues 35-208. Synonym: fibroblast growth factor-9, fgf9, gaf. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fgf9. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.20Å R-factor: 0.203 R-free: 0.226

Authors:

A.N.Plotnikov,A.V.Eliseenkova,O.A.Ibrahimi,M.A.Lemmon, M.Mohammadi

Key ref:

A.N.Plotnikov et al. (2001). Crystal structure of fibroblast growth factor 9 reveals regions implicated in dimerization and autoinhibition. J Biol Chem, 276, 4322-4329. PubMed id: 11060292 DOI: 10.1074/jbc.M006502200

Date:

19-Apr-01 Release date: 02-May-01

Protein chain

P31371  (FGF9_HUMAN) -  Glia-activating factor

Seq: 208 a.a.

Struc: 157 a.a.

 Gene Ontology (GO) functional annotation 

• Biochemical function: growth factor activity (1 term)

DOI no: 10.1074/jbc.M006502200

J Biol Chem 276:4322-4329 (2001)

PubMed id: 11060292

Crystal structure of fibroblast growth factor 9 reveals regions implicated in dimerization and autoinhibition.

A.N.Plotnikov, A.V.Eliseenkova, O.A.Ibrahimi, Z.Shriver, R.Sasisekharan, M.A.Lemmon, M.Mohammadi.

ABSTRACT

Fibroblast growth factors (FGFs) constitute a large family of heparin-binding growth factors with diverse biological activities. FGF9 was originally described as glia-activating factor and is expressed in the nervous system as a potent mitogen for glia cells. Unlike most FGFs, FGF9 forms dimers in solution with a K(d) of 680 nm. To elucidate the molecular mechanism of FGF9 dimerization, the crystal structure of FGF9 was determined at 2.2 A resolution. FGF9 adopts a beta-trefoil fold similar to other FGFs. However, unlike other FGFs, the N- and C-terminal regions outside the beta-trefoil core in FGF9 are ordered and involved in the formation of a 2-fold crystallographic dimer. A significant surface area (>2000 A(2)) is buried in the dimer interface that occludes a major receptor binding site of FGF9. Thus, we propose an autoinhibitory mechanism for FGF9 that is dependent on sequences outside of the beta-trefoil core. Moreover, a model is presented providing a molecular basis for the preferential affinity of FGF9 toward FGFR3.

Selected figure(s)

Figure 5.
Fig. 5. Structure-based sequence alignment of FGFs. Sequence alignment was performed using the CLUSTALW (41). All of the FGFs used in this alignment are human. The location and the length of the strands and helices are shown on the top of the sequence alignment. A period indicates sequence identity to FGF9. A dash represents a gap introduced to optimize the alignment. FGF9 residues that participate in dimerization are colored red. In blue are FGF9 residues that constitute the conventional low and high affinity heparin binding sites. FGF9 residues that localize to the periphery of the high affinity heparin-binding site and are predicted to form the distal and central heparin binding sites are colored green and yellow, respectively.

Figure 6.
Fig. 6. Mapping of receptor binding sites in FGF9. A, a model for the FGF9-FGFR1 structure was generated by superimposition of the C traces within the -trefoil of the FGF9 structure onto the corresponding C traces of FGF2 in the FGF2-FGFR1 structure. Orange, FGF9; green, D2; cyan, D3; gray, linker region; red, FGF9 regions that are in major clashes with FGFR1. B, stereo view of the receptor binding sites on FGF9. FGF9 residues are colored with respect to the FGFR regions with which they interact. FGF9 residues that interact with D2 are colored green, residues that interact with the linker region are colored gray, and residues that interact with D3 are colored cyan. FGF9 residues that interact with the C'- E loop in D3 of FGFR are colored purple. Color coding for atoms is the same as Fig. 4. This figure was created using Molscript and Raster3D.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 4322-4329) copyright 2001.

Figures were selected by an automated process.