PDBsum entry 1ihk

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Hormone/growth factor PDB id
Protein chain
157 a.a. *
PO4 ×2
Waters ×68
* Residue conservation analysis
PDB id:
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)
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
19-Apr-01     Release date:   02-May-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P31371  (FGF9_HUMAN) -  Fibroblast growth factor 9
208 a.a.
157 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     fibroblast growth factor receptor signaling pathway   1 term 
  Biochemical function     receptor binding     3 terms  


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.
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23403721 R.Goetz, and M.Mohammadi (2013).
Exploring mechanisms of FGF signalling through the lens of structural biology.
  Nat Rev Mol Cell Biol, 14, 166-180.  
20860061 S.Tulin, and A.Stathopoulos (2010).
Extending the family table: Insights from beyond vertebrates into the regulation of embryonic development by FGFs.
  Birth Defects Res C Embryo Today, 90, 214-227.  
19240749 D.Spicer (2009).
FGF9 on the move.
  Nat Genet, 41, 272-273.  
19564416 J.Kalinina, S.A.Byron, H.P.Makarenkova, S.K.Olsen, A.V.Eliseenkova, W.J.Larochelle, M.Dhanabal, S.Blais, D.M.Ornitz, L.A.Day, T.A.Neubert, P.M.Pollock, and M.Mohammadi (2009).
Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix.
  Mol Cell Biol, 29, 4663-4678.
PDB code: 3f1r
19219044 M.Harada, H.Murakami, A.Okawa, N.Okimoto, S.Hiraoka, T.Nakahara, R.Akasaka, Y.Shiraishi, N.Futatsugi, Y.Mizutani-Koseki, A.Kuroiwa, M.Shirouzu, S.Yokoyama, M.Taiji, S.Iseki, D.M.Ornitz, and H.Koseki (2009).
FGF9 monomer-dimer equilibrium regulates extracellular matrix affinity and tissue diffusion.
  Nat Genet, 41, 289-298.  
18165946 W.M.Abdel-Rahman, J.Kalinina, S.Shoman, S.Eissa, M.Ollikainen, O.Elomaa, A.V.Eliseenkova, R.Bützow, M.Mohammadi, and P.Peltomäki (2008).
Somatic FGF9 mutations in colorectal and endometrial carcinomas associated with membranous beta-catenin.
  Hum Mutat, 29, 390-397.  
17339340 R.Goetz, A.Beenken, O.A.Ibrahimi, J.Kalinina, S.K.Olsen, A.V.Eliseenkova, C.Xu, T.A.Neubert, F.Zhang, R.J.Linhardt, X.Yu, K.E.White, T.Inagaki, S.A.Kliewer, M.Yamamoto, H.Kurosu, Y.Ogawa, M.Kuro-o, B.Lanske, M.S.Razzaque, and M.Mohammadi (2007).
Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members.
  Mol Cell Biol, 27, 3417-3428.
PDB codes: 2p23 2p39
16834555 R.Sasisekharan, R.Raman, and V.Prabhakar (2006).
Glycomics approach to structure-function relationships of glycosaminoglycans.
  Annu Rev Biomed Eng, 8, 181-231.  
16315317 Y.Luo, S.Ye, M.Kan, and W.L.McKeehan (2006).
Structural specificity in a FGF7-affinity purified heparin octasaccharide required for formation of a complex with FGF7 and FGFR2IIIb.
  J Cell Biochem, 97, 1241-1258.  
15863029 M.Mohammadi, S.K.Olsen, and O.A.Ibrahimi (2005).
Structural basis for fibroblast growth factor receptor activation.
  Cytokine Growth Factor Rev, 16, 107-137.  
14502551 Y.Luo, H.H.Cho, and W.L.McKeehan (2003).
Biospecific extraction and neutralization of anticoagulant heparin with fibroblast growth factors (FGF).
  J Pharm Sci, 92, 2117-2127.  
12444071 M.Uzumcu, S.D.Westfall, K.A.Dirks, and M.K.Skinner (2002).
Embryonic testis cord formation and mesonephric cell migration requires the phosphotidylinositol 3-kinase signaling pathway.
  Biol Reprod, 67, 1927-1935.  
11486033 P.Bellosta, A.Iwahori, A.N.Plotnikov, A.V.Eliseenkova, C.Basilico, and M.Mohammadi (2001).
Identification of receptor and heparin binding sites in fibroblast growth factor 4 by structure-based mutagenesis.
  Mol Cell Biol, 21, 5946-5957.
PDB code: 1ijt
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.