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Transforming growth factor PDB id
1bmp
Jmol
Contents
Protein chain
104 a.a. *
* Residue conservation analysis
PDB id:
1bmp
Name: Transforming growth factor
Title: Bone morphogenetic protein-7
Structure: Bone morphogenetic protein-7. Chain: a. Synonym: osteogenic protein-1, hop-1, bmp-7. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: ovary. Gene: hop-1 cdna. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Other_details: reference, t.K. Sampath, et al. (1992) j. Bi 267, 20452-20362
Biol. unit: Dimer (from PDB file)
Resolution:
2.80Å     R-factor:   0.227     R-free:   0.308
Authors: D.L.Griffith,D.L.Scott
Key ref: D.L.Griffith et al. (1996). Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily. Proc Natl Acad Sci U S A, 93, 878-883. PubMed id: 8570652 DOI: 10.1073/pnas.93.2.878
Date:
14-Dec-95     Release date:   23-Jul-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P18075  (BMP7_HUMAN) -  Bone morphogenetic protein 7
Seq:
Struc: 		431 a.a.
104 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: 10.1073/pnas.93.2.878 Proc Natl Acad Sci U S A 93:878-883 (1996)
PubMed id: 8570652  
 
 
Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily.
D.L.Griffith, P.C.Keck, T.K.Sampath, D.C.Rueger, W.D.Carlson.
 
  ABSTRACT  
 
We report the three-dimensional structure of osteogenic protein 1 (OP-1, also known as bone morphogenetic protein 7) to 2.8-A resolution. OP-1 is a member of the transforming growth factor beta (TGF-beta) superfamily of proteins and is able to induce new bone formation in vivo. Members of this superfamily share sequence similarity in their C-terminal regions and are implicated in embryonic development and adult tissue repair. Our crystal structure makes possible the structural comparison between two members of the TGF-beta superfamily. We find that although there is limited sequence identity between OP-1 and TGF-beta 2, they share a common polypeptide fold. These results establish a basis for proposing the OP-1/TGF-beta 2 fold as the primary structural motif for the TGF-beta superfamily as a whole. Detailed comparison of the OP-1 and TGF-beta 2 structures has revealed striking differences that provide insights into how these growth factors interact with their receptors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21079644 D.J.Hunter (2011).
Pharmacologic therapy for osteoarthritis--the era of disease modification.
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20545624 C.C.Rider, and B.Mulloy (2010).
Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists.
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20932341 D.J.Hunter, M.C.Pike, B.L.Jonas, E.Kissin, J.Krop, and T.McAlindon (2010).
Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis.
  BMC Musculoskelet Disord, 11, 232.  
19875899 F.Otsuka (2010).
Multiple endocrine regulation by bone morphogenetic protein system.
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20048150 K.Song, C.Krause, S.Shi, M.Patterson, R.Suto, L.Grgurevic, S.Vukicevic, M.van Dinther, D.Falb, P.Ten Dijke, and M.H.Alaoui-Ismaili (2010).
Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity.
  J Biol Chem, 285, 12169-12180.  
20661431 Q.Zhang, Y.Shi, J.Wada, S.M.Malakauskas, M.Liu, Y.Ren, C.Du, H.Duan, Y.Li, Y.Li, and Y.Zhang (2010).
In vivo delivery of Gremlin siRNA plasmid reveals therapeutic potential against diabetic nephropathy by recovering bone morphogenetic protein-7.
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19926516 J.Nickel, W.Sebald, J.C.Groppe, and T.D.Mueller (2009).
Intricacies of BMP receptor assembly.
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19910235 M.H.Alaoui-Ismaili, and D.Falb (2009).
Design of second generation therapeutic recombinant bone morphogenetic proteins.
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19726563 N.Y.Lee, K.C.Kirkbride, R.D.Sheu, and G.C.Blobe (2009).
The transforming growth factor-beta type III receptor mediates distinct subcellular trafficking and downstream signaling of activin-like kinase (ALK)3 and ALK6 receptors.
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18596525 D.Benglis, M.Y.Wang, and A.D.Levi (2008).
A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery.
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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).
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18283415 W.Yang, L.Cao, W.Liu, L.Jiang, M.Sun, D.Zhang, S.Wang, W.H.Lo, Y.Luo, and X.Zhang (2008).
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17136606 M.R.Towler, A.Wren, N.Rushe, J.Saunders, N.M.Cummins, and P.M.Jakeman (2007).
Raman spectroscopy of the human nail: a potential tool for evaluating bone health?
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17089091 Y.Haramoto, S.Takahashi, and M.Asashima (2007).
Monomeric mature protein of Nodal-related 3 activates Xbra expression.
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16488673 W.Zhu, J.Kim, C.Cheng, B.A.Rawlins, O.Boachie-Adjei, R.G.Crystal, and C.Hidaka (2006).
Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro.
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16245174 B.Klösch, W.Fürst, R.Kneidinger, M.Schuller, B.Rupp, A.Banerjee, and H.Redl (2005).
Expression and purification of biologically active rat bone morphogenetic protein-4 produced as inclusion bodies in recombinant Escherichia coli.
  Biotechnol Lett, 27, 1559-1564.  
15948132 H.H.Keah, and M.T.Hearn (2005).
A molecular recognition paradigm: promiscuity associated with the ligand-receptor interactions of the activin members of the TGF-beta superfamily.
  J Mol Recognit, 18, 385-403.  
15917343 S.A.Pangas, and M.M.Matzuk (2005).
The art and artifact of GDF9 activity: cumulus expansion and the cumulus expansion-enabling factor.
  Biol Reprod, 73, 582-585.  
  16508114 T.D.Mueller, M.Gottermeier, W.Sebald, and J.Nickel (2005).
Crystallization and preliminary X-ray diffraction analysis of human growth and differentiation factor 5 (GDF-5).
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15599282 D.H.Kim, T.A.Jahng, T.S.Fu, H.Y.Zhang, and S.A.Novak (2004).
Evaluation of HealosMP52 osteoinductive bone graft for instrumented lumbar intertransverse process fusion in sheep.
  Spine, 29, 2800-2808.  
15509223 D.W.McCauley, M.Bronner-Fraser, and M.Bronner-Fraser (2004).
Conservation and divergence of BMP2/4 genes in the lamprey: expression and phylogenetic analysis suggest a single ancestral vertebrate gene.
  Evol Dev, 6, 411-422.  
14627550 J.P.Hanrahan, S.M.Gregan, P.Mulsant, M.Mullen, G.H.Davis, R.Powell, and S.M.Galloway (2004).
Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries).
  Biol Reprod, 70, 900-909.  
  14746809 M.de Caestecker (2004).
The transforming growth factor-beta superfamily of receptors.
  Cytokine Growth Factor Rev, 15, 1.  
15473835 S.J.Lee (2004).
Regulation of muscle mass by myostatin.
  Annu Rev Cell Dev Biol, 20, 61-86.  
15064755 S.Keller, J.Nickel, J.L.Zhang, W.Sebald, and T.D.Mueller (2004).
Molecular recognition of BMP-2 and BMP receptor IA.
  Nat Struct Mol Biol, 11, 481-488.
PDB codes: 1reu 1rew
15449706 W.Sebald, J.Nickel, J.L.Zhang, and T.D.Mueller (2004).
Molecular recognition in bone morphogenetic protein (BMP)/receptor interaction.
  Biol Chem, 385, 697-710.  
12919870 A.Chhabra, D.Tsou, R.T.Clark, V.Gaschen, E.B.Hunziker, and B.Mikic (2003).
GDF-5 deficiency in mice delays Achilles tendon healing.
  J Orthop Res, 21, 826-835.  
12667445 J.Greenwald, J.Groppe, P.Gray, E.Wiater, W.Kwiatkowski, W.Vale, and S.Choe (2003).
The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly.
  Mol Cell, 11, 605-617.
PDB codes: 1lx5 1lxi
14745974 R.Serra, and C.Chang (2003).
TGF-beta signaling in human skeletal and patterning disorders.
  Birth Defects Res C Embryo Today, 69, 333-351.  
12900894 S.A.Al-Yahyaee, M.N.Al-Kindi, O.Habbal, and D.S.Kumar (2003).
Clinical and molecular analysis of Grebe acromesomelic dysplasia in an Omani family.
  Am J Med Genet A, 121, 9.  
  12798347 S.Chubinskaya, and K.E.Kuettner (2003).
Regulation of osteogenic proteins by chondrocytes.
  Int J Biochem Cell Biol, 35, 1323-1340.  
12660162 T.B.Thompson, T.K.Woodruff, and T.S.Jardetzky (2003).
Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions.
  EMBO J, 22, 1555-1566.
PDB codes: 1nys 1nyu
14559178 W.Sebald, and T.D.Mueller (2003).
The interaction of BMP-7 and ActRII implicates a new mode of receptor assembly.
  Trends Biochem Sci, 28, 518-521.  
  12440701 A.Mehra, and J.L.Wrana (2002).
TGF-beta and the Smad signal transduction pathway.
  Biochem Cell Biol, 80, 605-622.  
12357473 D.B.Everman, C.F.Bartels, Y.Yang, N.Yanamandra, F.R.Goodman, J.R.Mendoza-Londono, R.Savarirayan, S.M.White, J.M.Graham, R.P.Gale, E.Svarch, W.G.Newman, A.R.Kleckers, C.A.Francomano, V.Govindaiah, L.Singh, S.Morrison, J.T.Thomas, and M.L.Warman (2002).
The mutational spectrum of brachydactyly type C.
  Am J Med Genet, 112, 291-296.  
12478285 J.Groppe, J.Greenwald, E.Wiater, J.Rodriguez-Leon, A.N.Economides, W.Kwiatkowski, M.Affolter, W.W.Vale, J.C.Belmonte, and S.Choe (2002).
Structural basis of BMP signalling inhibition by the cystine knot protein Noggin.
  Nature, 420, 636-642.
PDB code: 1m4u
11850637 P.J.Hart, S.Deep, A.B.Taylor, Z.Shu, C.S.Hinck, and A.P.Hinck (2002).
Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex.
  Nat Struct Biol, 9, 203-208.
PDB code: 1ktz
11774231 H.H.Keah, N.Allen, R.Clay, R.I.Boysen, T.Warner, and M.T.Hearn (2001).
Total chemical synthesis of human activin beta(A)[12-116] and related large-loop polypeptides.
  Biopolymers, 60, 279-289.  
11746688 P.K.Shah, C.M.Buslje, and R.Sowdhamini (2001).
Structural determinants of binding and specificity in transforming growth factor-receptor interactions.
  Proteins, 45, 408-420.  
11141057 W.D.Fairlie, P.K.Russell, W.M.Wu, A.G.Moore, H.P.Zhang, P.K.Brown, A.R.Bauskin, and S.N.Breit (2001).
Epitope mapping of the transforming growth factor-beta superfamily protein, macrophage inhibitory cytokine-1 (MIC-1): identification of at least five distinct epitope specificities.
  Biochemistry, 40, 65-73.  
10992432 A.H.Reddi (2000).
Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials.
  Tissue Eng, 6, 351-359.  
11080174 M.Böttner, K.Krieglstein, and K.Unsicker (2000).
The transforming growth factor-betas: structure, signaling, and roles in nervous system development and functions.
  J Neurochem, 75, 2227-2240.  
10844590 P.Ducy, and G.Karsenty (2000).
The family of bone morphogenetic proteins.
  Kidney Int, 57, 2207-2214.  
10880444 T.Kirsch, J.Nickel, and W.Sebald (2000).
BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II.
  EMBO J, 19, 3314-3324.  
  10353905 K.A.Wharton, J.M.Cook, S.Torres-Schumann, K.de Castro, E.Borod, and D.A.Phillips (1999).
Genetic analysis of the bone morphogenetic protein-related gene, gbb, identifies multiple requirements during Drosophila development.
  Genetics, 152, 629-640.  
9528003 A.H.Reddi (1998).
Role of morphogenetic proteins in skeletal tissue engineering and regeneration.
  Nat Biotechnol, 16, 247-252.  
9759503 J.Massagué (1998).
TGF-beta signal transduction.
  Annu Rev Biochem, 67, 753-791.  
9469567 T.Ebendal, H.Bengtsson, and S.Söderström (1998).
Bone morphogenetic proteins and their receptors: potential functions in the brain.
  J Neurosci Res, 51, 139-146.  
9664686 T.Katagiri, S.Boorla, J.L.Frendo, B.L.Hogan, and G.Karsenty (1998).
Skeletal abnormalities in doubly heterozygous Bmp4 and Bmp7 mice.
  Dev Genet, 22, 340-348.  
9356471 A.C.McPherron, and S.J.Lee (1997).
Double muscling in cattle due to mutations in the myostatin gene.
  Proc Natl Acad Sci U S A, 94, 12457-12461.  
9187648 C.Eigenbrot, and N.Gerber (1997).
X-ray structure of glial cell-derived neurotrophic factor at 1.9 A resolution and implications for receptor binding.
  Nat Struct Biol, 4, 435-438.
PDB code: 1agq
9442904 H.Lin (1997).
The tao of stem cells in the germline.
  Annu Rev Genet, 31, 455-491.  
9288098 J.T.Thomas, M.W.Kilpatrick, K.Lin, L.Erlacher, P.Lembessis, T.Costa, P.Tsipouras, and F.P.Luyten (1997).
Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1.
  Nat Genet, 17, 58-64.  
  9071596 P.C.Marker, K.Seung, A.E.Bland, L.B.Russell, and D.M.Kingsley (1997).
Spectrum of Bmp5 mutations from germline mutagenesis experiments in mice.
  Genetics, 145, 435-443.  
9395284 R.Derynck, and X.H.Feng (1997).
TGF-beta receptor signaling.
  Biochim Biophys Acta, 1333, F105-F150.  
9207067 Y.A.Muller, B.Li, H.W.Christinger, J.A.Wells, B.C.Cunningham, and A.M.de Vos (1997).
Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site.
  Proc Natl Acad Sci U S A, 94, 7192-7197.
PDB code: 1vpf
  9351807 Y.A.Muller, H.W.Christinger, B.A.Keyt, and A.M.de Vos (1997).
The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 A resolution: multiple copy flexibility and receptor binding.
  Structure, 5, 1325-1338.
PDB code: 2vpf
  8791534 B.L.Hogan (1996).
Bone morphogenetic proteins in development.
  Curr Opin Genet Dev, 6, 432-438.  
9631089 M.W.Szkudlinski, N.G.Teh, M.Grossmann, J.E.Tropea, and B.D.Weintraub (1996).
Engineering human glycoprotein hormone superactive analogues.
  Nat Biotechnol, 14, 1257-1263.  
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 codes are shown on the right.