PDBsum entry 2r52

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Cytokine PDB id
Jmol PyMol
Protein chains
105 a.a. *
IPA ×10
Waters ×53
* Residue conservation analysis
PDB id:
Name: Cytokine
Title: Crystal structure analysis of bone morphogenetic protein-6 (bmp-6)
Structure: Bone morphogenetic protein 6. Chain: a, b. Fragment: mature part (residues 375-513). Synonym: bmp-6. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: bmp6, vgr. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.50Å     R-factor:   0.235     R-free:   0.270
Authors: T.D.Mueller,W.Sebald,S.Saremba
Key ref: S.Saremba et al. (2007). Type I receptor binding of bone morphogenetic protein 6 is dependent on N-glycosylation of the ligand. Febs J, 275, 172-183. PubMed id: 18070108 DOI: 10.1111/j.1742-4658.2007.06187.x
03-Sep-07     Release date:   15-Jan-08    
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Protein chains
Pfam   ArchSchema ?
P22004  (BMP6_HUMAN) -  Bone morphogenetic protein 6
513 a.a.
105 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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


DOI no: 10.1111/j.1742-4658.2007.06187.x Febs J 275:172-183 (2007)
PubMed id: 18070108  
Type I receptor binding of bone morphogenetic protein 6 is dependent on N-glycosylation of the ligand.
S.Saremba, J.Nickel, A.Seher, A.Kotzsch, W.Sebald, T.D.Mueller.
Bone morphogenetic proteins (BMPs), together with transforming growth factor (TGF)-beta and activins/inhibins, constitute the TGF-beta superfamily of ligands. This superfamily is formed by more than 30 structurally related secreted proteins. The crystal structure of human BMP-6 was determined to a resolution of 2.1 A; the overall structure is similar to that of other TGF-beta superfamily ligands, e.g. BMP-7. The asymmetric unit contains the full dimeric BMP-6, indicating possible asymmetry between the two monomeric subunits. Indeed, the conformation of several loops differs between both monomers. In particular, the prehelix loop, which plays a crucial role in the type I receptor interactions of BMP-2, adopts two rather different conformations in BMP-6, indicating possible dynamic flexibility of the prehelix loop in its unbound conformation. Flexibility of this loop segment has been discussed as an important feature required for promiscuous binding of different type I receptors to BMPs. Further studies investigating the interaction of BMP-6 with different ectodomains of type I receptors revealed that N-glycosylation at Asn73 of BMP-6 in the wrist epitope is crucial for recognition by the activin receptor type I. In the absence of the carbohydrate moiety, activin receptor type I-mediated signaling of BMP-6 is totally diminished. Thus, flexibility within the binding epitope of BMP-6 and an unusual recognition motif, i.e. an N-glycosylation motif, possibly play an important role in type I receptor specificity of BMP-6.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21308845 A.Kotzsch, E.Vernet, M.Hammarström, J.Berthelsen, J.Weigelt, S.Gräslund, and M.Sundström (2011).
A secretory system for bacterial production of high-profile protein targets.
  Protein Sci, 20, 597-609.  
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.  
20844121 L.Crews, A.Adame, C.Patrick, A.Delaney, E.Pham, E.Rockenstein, L.Hansen, and E.Masliah (2010).
Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis.
  J Neurosci, 30, 12252-12262.  
19786029 S.Arndt, U.Maegdefrau, C.Dorn, K.Schardt, C.Hellerbrand, and A.K.Bosserhoff (2010).
Iron-induced expression of bone morphogenic protein 6 in intestinal cells is the main regulator of hepatic hepcidin expression in vivo.
  Gastroenterology, 138, 372-382.  
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
19855014 D.Umulis, M.B.O'Connor, and S.S.Blair (2009).
The extracellular regulation of bone morphogenetic protein signaling.
  Development, 136, 3715-3728.  
19543302 J.D.Yan, S.Yang, J.Zhang, and T.H.Zhu (2009).
BMP6 reverses TGF-beta1-induced changes in HK-2 cells: implications for the treatment of renal fibrosis.
  Acta Pharmacol Sin, 30, 994.  
19644449 J.N.Cash, C.A.Rejon, A.C.McPherron, D.J.Bernard, and T.B.Thompson (2009).
The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding.
  EMBO J, 28, 2662-2676.
PDB code: 3hh2
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.  
19245827 J.Yan, S.Yang, J.Zhang, C.Zhai, and T.Zhu (2009).
BMP6 attenuates oxidant injury in HK-2 cells via Smad-dependent HO-1 induction.
  Free Radic Biol Med, 46, 1275-1282.  
19735544 K.Heinecke, A.Seher, W.Schmitz, T.D.Mueller, W.Sebald, and J.Nickel (2009).
Receptor oligomerization and beyond: a case study in bone morphogenetic proteins.
  BMC Biol, 7, 59.  
19910235 M.H.Alaoui-Ismaili, and D.Falb (2009).
Design of second generation therapeutic recombinant bone morphogenetic proteins.
  Cytokine Growth Factor Rev, 20, 501-507.  
19900832 S.Vukicevic, and L.Grgurevic (2009).
BMP-6 and mesenchymal stem cell differentiation.
  Cytokine Growth Factor Rev, 20, 441-448.  
19801543 U.M.Polanska, L.Duchesne, J.C.Harries, D.G.Fernig, and T.K.Kinnunen (2009).
N-Glycosylation regulates fibroblast growth factor receptor/EGL-15 activity in Caenorhabditis elegans in vivo.
  J Biol Chem, 284, 33030-33039.  
18621057 G.Sengle, R.N.Ono, K.M.Lyons, H.P.Bächinger, and L.Y.Sakai (2008).
A new model for growth factor activation: type II receptors compete with the prodomain for BMP-7.
  J Mol Biol, 381, 1025-1039.  
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.