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Growth factor PDB id
2bhk
Jmol
Contents
Protein chain
105 a.a. *
Ligands
IPA ×5
Waters ×72
* Residue conservation analysis
PDB id:
2bhk
Name: Growth factor
Title: Crystal structure of human growth and differentiation factor 5 (gdf5)
Structure: Growth differentiation factor 5. Chain: a. Synonym: gdf-5, cartilage-derived morphogenetic protein 1, cdmp-1. Engineered: yes. Other_details: interchain disulfide link between two crystallographically related monomers
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.4Å     R-factor:   0.168     R-free:   0.220
Authors: H.Schreuder,A.Liesum,J.Pohl,M.Kruse,M.Koyama
Key ref: H.Schreuder et al. (2005). Crystal structure of recombinant human growth and differentiation factor 5: evidence for interaction of the type I and type II receptor-binding sites. Biochem Biophys Res Commun, 329, 1076-1086. PubMed id: 15752764 DOI: 10.1016/j.bbrc.2005.02.078
Date:
12-Jan-05     Release date:   11-Mar-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P43026  (GDF5_HUMAN) -  Growth/differentiation factor 5
Seq:
Struc: 		501 a.a.
105 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biochemical function     growth factor activity     1 term  

 

 
DOI no: 10.1016/j.bbrc.2005.02.078 Biochem Biophys Res Commun 329:1076-1086 (2005)
PubMed id: 15752764  
 
 
Crystal structure of recombinant human growth and differentiation factor 5: evidence for interaction of the type I and type II receptor-binding sites.
H.Schreuder, A.Liesum, J.Pohl, M.Kruse, M.Koyama.
 
  ABSTRACT  
 
The crystal structure of human growth differentiation factor 5 (GDF5) was solved at 2.4A resolution. The structure is very similar to the structure of bone morphogenetic factor 7 (BMP7) and consists of two banana-shaped monomers, linked via a disulfide bridge. The crystal packing of GDF5 is the same as the crystal packing of BMP7. This is highly unusual since only 25-30% of the crystal contacts involve identical residues. Analysis of the crystal packing revealed that residues of the type I receptor epitope are binding to residues of the type II receptor-binding epitope. The fact that for both BMP family members the type I and type II receptor-binding sites interact suggests that the complementary sites on the receptors may interact as well, suggesting a way how preformed receptor heterodimers may form, similar to the preformed receptors observed for the erythropoietin receptor and the BMP2 receptors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20683927 A.M.Byrnes, L.Racacho, S.M.Nikkel, F.Xiao, H.MacDonald, T.M.Underhill, and D.E.Bulman (2010).
Mutations in GDF5 presenting as semidominant brachydactyly A1.
  Hum Mutat, 31, 1155-1162.  
20545624 C.C.Rider, and B.Mulloy (2010).
Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists.
  Biochem J, 429, 1.  
20161792 C.S.Starck, and A.J.Sutherland-Smith (2010).
Cytotoxic aggregation and amyloid formation by the myostatin precursor protein.
  PLoS One, 5, e9170.  
20170953 P.Kasten, I.Beyen, D.Bormann, R.Luginbühl, F.Plöger, and W.Richter (2010).
The effect of two point mutations in GDF-5 on ectopic bone formation in a beta-tricalciumphosphate scaffold.
  Biomaterials, 31, 3878-3884.  
19267859 A.J.Bella, G.Lin, C.S.Lin, D.R.Hickling, C.Morash, and T.F.Lue (2009).
Nerve growth factor modulation of the cavernous nerve response to injury.
  J Sex Med, 6, 347-352.  
19229295 A.Kotzsch, J.Nickel, A.Seher, W.Sebald, and T.D.Müller (2009).
Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity.
  EMBO J, 28, 937-947.
PDB code: 3evs
19926516 J.Nickel, W.Sebald, J.C.Groppe, and T.D.Mueller (2009).
Intricacies of BMP receptor assembly.
  Cytokine Growth Factor Rev, 20, 367-377.  
19193648 K.L.Walton, Y.Makanji, M.C.Wilce, K.L.Chan, D.M.Robertson, and C.A.Harrison (2009).
A common biosynthetic pathway governs the dimerization and secretion of inhibin and related transforming growth factor beta (TGFbeta) ligands.
  J Biol Chem, 284, 9311-9320.  
19956691 P.Seemann, A.Brehm, J.König, C.Reissner, S.Stricker, P.Kuss, J.Haupt, S.Renninger, J.Nickel, W.Sebald, J.C.Groppe, F.Plöger, J.Pohl, M.Schmidt-von Kegler, M.Walther, I.Gassner, C.Rusu, A.R.Janecke, K.Dathe, and S.Mundlos (2009).
Mutations in GDF5 reveal a key residue mediating BMP inhibition by NOGGIN.
  PLoS Genet, 5, e1000747.  
19208630 V.Veverka, A.J.Henry, P.M.Slocombe, A.Ventom, B.Mulloy, F.W.Muskett, M.Muzylak, K.Greenslade, A.Moore, L.Zhang, J.Gong, X.Qian, C.Paszty, R.J.Taylor, M.K.Robinson, and M.D.Carr (2009).
Characterization of the Structural Features and Interactions of Sclerostin: MOLECULAR INSIGHT INTO A KEY REGULATOR OF Wnt-MEDIATED BONE FORMATION.
  J Biol Chem, 284, 10890-10900.
PDB code: 2k8p
18569021 G.Feng, Y.Wan, G.Balian, C.T.Laurencin, and X.Li (2008).
Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells.
  Growth Factors, 26, 132-142.  
18180771 P.Basile, T.Dadali, J.Jacobson, S.Hasslund, M.Ulrich-Vinther, K.Søballe, Y.Nishio, M.H.Drissi, H.N.Langstein, D.J.Mitten, R.J.O'Keefe, E.M.Schwarz, and H.A.Awad (2008).
Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery.
  Mol Ther, 16, 466-473.  
18293427 P.C.Bessa, M.Casal, and R.L.Reis (2008).
Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts).
  J Tissue Eng Regen Med, 2, 1.  
18564148 T.M.Fandel, A.J.Bella, G.Lin, K.Tantiwongse, C.S.Lin, J.Pohl, and T.F.Lue (2008).
Intracavernous growth differentiation factor-5 therapy enhances the recovery of erectile function in a rat model of cavernous nerve injury.
  J Sex Med, 5, 1866-1875.  
18397882 Y.Makanji, K.L.Walton, M.C.Wilce, K.L.Chan, D.M.Robertson, and C.A.Harrison (2008).
Suppression of inhibin A biological activity by alterations in the binding site for betaglycan.
  J Biol Chem, 283, 16743-16751.  
17668388 K.Lehmann, P.Seemann, F.Silan, T.O.Goecke, S.Irgang, K.W.Kjaer, S.Kjaergaard, M.J.Mahoney, S.Morlot, C.Reissner, B.Kerr, A.O.Wilkie, and S.Mundlos (2007).
A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN.
  Am J Hum Genet, 81, 388-396.  
16606344 C.Sieber, F.Plöger, R.Schwappacher, R.Bechtold, M.Hanke, S.Kawai, Y.Muraki, M.Katsuura, M.Kimura, M.M.Rechtman, Y.I.Henis, J.Pohl, and P.Knaus (2006).
Monomeric and dimeric GDF-5 show equal type I receptor binding and oligomerization capability and have the same biological activity.
  Biol Chem, 387, 451-460.  
16014698 K.W.Kjaer, H.Eiberg, L.Hansen, C.B.van der Hagen, K.Rosendahl, N.Tommerup, and S.Mundlos (2006).
A mutation in the receptor binding site of GDF5 causes Mohr-Wriedt brachydactyly type A2.
  J Med Genet, 43, 225-231.  
16892395 X.Wang, F.Xiao, Q.Yang, B.Liang, Z.Tang, L.Jiang, Q.Zhu, W.Chang, J.Jiang, C.Jiang, X.Ren, J.Y.Liu, Q.K.Wang, and M.Liu (2006).
A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families.
  Am J Med Genet A, 140, 1846-1853.  
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.