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Transferase PDB id
2goo
Jmol
Contents
Protein chains
103 a.a. *
85 a.a. *
92 a.a. *
Ligands
NDG ×4
Waters ×327
* Residue conservation analysis
PDB id:
2goo
Name: Transferase
Title: Ternary complex of bmp-2 bound to bmpr-ia-ecd and actrii-ecd
Structure: Bone morphogenetic protein 2. Chain: a, d. Fragment: residues 283-396. Synonym: bmp-2, bmp-2a. Engineered: yes. Bone morphogenetic protein receptor type ia. Chain: b, e. Fragment: residues 24-152. Synonym: serine/threonine-protein kinase receptor r5, skr5,
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: bmp2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: bmpr1a. Mus musculus. House mouse.
Biol. unit: Hexamer (from PQS)
Resolution:
2.20Å     R-factor:   0.224     R-free:   0.259
Authors: G.P.Allendorph,S.Choe
Key ref:
G.P.Allendorph et al. (2006). Structure of the ternary signaling complex of a TGF-beta superfamily member. Proc Natl Acad Sci U S A, 103, 7643-7648. PubMed id: 16672363 DOI: 10.1073/pnas.0602558103
Date:
13-Apr-06     Release date:   09-May-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P12643  (BMP2_HUMAN) -  Bone morphogenetic protein 2
Seq:
Struc: 		396 a.a.
103 a.a.
Protein chains
Pfam   ArchSchema ?
P36894  (BMR1A_HUMAN) -  Bone morphogenetic protein receptor type-1A
Seq:
Struc: 		 
Seq:
Struc: 		532 a.a.
85 a.a.
Protein chains
Pfam   ArchSchema ?
P27038  (AVR2A_MOUSE) -  Activin receptor type-2A
Seq:
Struc: 		513 a.a.
92 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains B, C, E, F: E.C.2.7.11.30  - Receptor protein serine/threonine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [receptor-protein] = ADP + [receptor-protein] phosphate
ATP
 + [receptor-protein]
 =
ADP
Bound ligand (Het Group name = NDG)
matches with 40.00% similarity 		+ [receptor-protein] phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     transmembrane receptor protein serine/threonine kinase signaling pathway   2 terms 
  Biochemical function     growth factor activity     6 terms  

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.0602558103 Proc Natl Acad Sci U S A 103:7643-7648 (2006)
PubMed id: 16672363  
 
 
Structure of the ternary signaling complex of a TGF-beta superfamily member.
G.P.Allendorph, W.W.Vale, S.Choe.
 
  ABSTRACT  
 
The crystal structure of the complete signaling complex formed between bone morphogenetic protein 2 (BMP-2) and the extracellular domains (ECDs) of its type I receptor [bone morphogenetic protein receptor type Ia (BMPR-Ia)-ECD] and its type II receptor [activin receptor type II (ActRII)-ECD] shows two fundamental structural constraints for receptor assembly. First, the homodimeric BMP-2 ligand assembles two pairs of each receptor symmetrically, where each of the receptor ECDs does not make physical contact. Therefore, conformational communication between receptor ECDs, if any, should be propagated through the central ligand. Second, the type I and II receptor interfaces of the complex, when compared with those of binary complexes such as BMP-2/BMPR Ia-ECD, BMP-7/ActRII-ECD, and activin/ActRIIb-ECD, respectively, show there are common sets of positions repeatedly used by both ligands and receptors. Therefore, specificity-determining amino acid differences at the receptor interfaces should also account for the disparity in affinity of individual receptors for different ligand subunits. We find that a specific mutation to BMP-2 increases its affinity to ActRII-ECD by 5-fold. These results together establish that the specific signaling output is largely determined by two variables, the ligand-receptor pair identity and the mode of cooperative assembly of relevant receptors governed by the ligand flexibility in a membrane-restricted manner.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Ternary complex of BMP-2/BMPR-Ia-ECD/ActRII-ECD shows noncontacting assembly of receptors. (a) Ternary complex of BMP-2/BMPR-Ia-ECD/ActRII-ECD as seen in the membrane. BMP-2 dimer subunits are shown in red and orange, displaying the butterfly conformation. The two BMPR-Ia-ECDs are shown in blue, and the ActRII-ECDs are shown in green. Dashed lines represent C-terminal residues connecting to the membrane-spanning segments of the receptors. Cystines are shown as yellow spheres. (b) A top view of the complex. The color scheme is the same as in a. Labeled are -helix 3 of BMP-2 and -helix 1 of BMPR-Ia. (Inset) The M loop of the ActRII from BMP-2/ActRII-ECD/BMPR-Ia-ECD (green), BMP-7/ActRII-ECD (blue), and activin/ActRIIb-ECD (red) structures. 		Figure 2.
Fig. 2. Ligand-binding interfaces of type II receptors show a nearly common set of interface positions. Peeled-away interfaces of BMP-2/ActRII-ECD (a), BMP-7/ActRII-ECD (b), and activin/ActRIIb-ECD (c) pairs shown as space-filling model. Orientation is as in Fig. 1a. Colored are those in contact between the two chains, for identical (pink), highly conserved (green), and nonconserved (blue) residues. Asterisks denote reference contact points between the two molecules. (d) List of the five identical residues in ActRII and ActRIIb and their contacting amino acids on three ligands.
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20567515 E.Valera, M.J.Isaacs, Y.Kawakami, J.C.Izpisúa Belmonte, and S.Choe (2010).
BMP-2/6 heterodimer is more effective than BMP-2 or BMP-6 homodimers as inductor of differentiation of human embryonic stem cells.
  PLoS One, 5, e11167.  
20674464 J.W.Lowery, and M.P.de Caestecker (2010).
BMP signaling in vascular development and disease.
  Cytokine Growth Factor Rev, 21, 287-298.  
19762341 K.Miyazono, Y.Kamiya, and M.Morikawa (2010).
Bone morphogenetic protein receptors and signal transduction.
  J Biochem, 147, 35-51.  
20890540 L.Li, B.P.Orner, T.Huang, A.P.Hinck, and L.L.Kiessling (2010).
Peptide ligands that use a novel binding site to target both TGF-β receptors.
  Mol Biosyst, 6, 2392-2402.  
  20927405 S.Harth, A.Kotzsch, J.Hu, W.Sebald, and T.D.Mueller (2010).
A selection fit mechanism in BMP receptor IA as a possible source for BMP ligand-receptor promiscuity.
  PLoS One, 5, 0.
PDB code: 3nh7
20861306 W.J.Kuo, M.A.Digman, and A.D.Lander (2010).
Heparan sulfate acts as a bone morphogenetic protein coreceptor by facilitating ligand-induced receptor hetero-oligomerization.
  Mol Biol Cell, 21, 4028-4041.  
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
19457927 C.Belville, J.D.Maréchal, S.Pennetier, P.Carmillo, L.Masgrau, L.Messika-Zeitoun, J.Galey, G.Machado, D.Treton, J.Gonzalès, J.Y.Picard, N.Josso, R.L.Cate, and N.di Clemente (2009).
Natural mutations of the anti-Mullerian hormone type II receptor found in persistent Mullerian duct syndrome affect ligand binding, signal transduction and cellular transport.
  Hum Mol Genet, 18, 3002-3013.  
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.  
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.  
  19806034 L.Wang (2009).
Towards revealing the structure of bacterial inclusion bodies.
  Prion, 3, 139-145.  
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.  
19951429 N.Feiner, G.Begemann, A.J.Renz, A.Meyer, and S.Kuraku (2009).
The origin of bmp16, a novel Bmp2/4 relative, retained in teleost fish genomes.
  BMC Evol Biol, 9, 277.  
19900832 S.Vukicevic, and L.Grgurevic (2009).
BMP-6 and mesenchymal stem cell differentiation.
  Cytokine Growth Factor Rev, 20, 441-448.  
19273500 Y.Xia, and A.L.Schneyer (2009).
The biology of activin: recent advances in structure, regulation and function.
  J Endocrinol, 202, 1.  
18485004 A.Galat, G.Gross, P.Drevet, A.Sato, and A.Ménez (2008).
Conserved structural determinants in three-fingered protein domains.
  FEBS J, 275, 3207-3225.  
17943733 C.Busch, U.Drews, S.R.Eisele, C.Garbe, and M.Oppitz (2008).
Noggin blocks invasive growth of murine B16-F1 melanoma cells in the optic cup of the chick embryo.
  Int J Cancer, 122, 526-533.  
18500331 D.E.Klein, S.E.Stayrook, F.Shi, K.Narayan, and M.A.Lemmon (2008).
Structural basis for EGFR ligand sequestration by Argos.
  Nature, 453, 1271-1275.
PDB codes: 3c9a 3ca7 3cgu
18335997 F.Yang, A.P.West, G.P.Allendorph, S.Choe, and P.J.Bjorkman (2008).
Neogenin interacts with hemojuvelin through its two membrane-proximal fibronectin type III domains.
  Biochemistry, 47, 4237-4245.  
18243111 J.Groppe, C.S.Hinck, P.Samavarchi-Tehrani, C.Zubieta, J.P.Schuermann, A.B.Taylor, P.M.Schwarz, J.L.Wrana, and A.P.Hinck (2008).
Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding.
  Mol Cell, 29, 157-168.
PDB code: 2pjy
18684013 L.Wang, S.K.Maji, M.R.Sawaya, D.Eisenberg, and R.Riek (2008).
Bacterial inclusion bodies contain amyloid-like structure.
  PLoS Biol, 6, e195.  
  18391434 L.Y.Qiu, J.L.Zhang, A.Kotzsch, W.Sebald, and T.D.Mueller (2008).
Crystallization and preliminary X-ray analysis of the complex of the first von Willebrand type C domain bound to bone morphogenetic protein 2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 307-312.  
18474281 M.E.Carlson, H.S.Silva, and I.M.Conboy (2008).
Aging of signal transduction pathways, and pathology.
  Exp Cell Res, 314, 1951-1961.  
18768470 R.Stamler, H.T.Keutmann, Y.Sidis, C.Kattamuri, A.Schneyer, and T.B.Thompson (2008).
The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity.
  J Biol Chem, 283, 32831-32838.
PDB code: 3b4v
18000526 B.Schmierer, and C.S.Hill (2007).
TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.
  Nat Rev Mol Cell Biol, 8, 970-982.  
17295905 D.Weber, A.Kotzsch, J.Nickel, S.Harth, A.Seher, U.Mueller, W.Sebald, and T.D.Mueller (2007).
A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor.
  BMC Struct Biol, 7, 6.
PDB codes: 2h62 2h64
17643432 P.T.Loverde, A.Osman, and A.Hinck (2007).
Schistosoma mansoni: TGF-beta signaling pathways.
  Exp Parasitol, 117, 304-317.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
17146441 T.Shimanuki, T.Hara, T.Furuya, T.Imamura, and K.Miyazono (2007).
Modulation of the functional binding sites for TGF-beta on the type II receptor leads to suppression of TGF-beta signaling.
  Oncogene, 26, 3311-3320.  
17040568 D.J.Bernard, K.B.Lee, and M.M.Santos (2006).
Activin B can signal through both ALK4 and ALK7 in gonadotrope cells.
  Reprod Biol Endocrinol, 4, 52.  
16765900 X.Wang, R.H.Baloh, J.Milbrandt, and K.C.Garcia (2006).
Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors.
  Structure, 14, 1083-1092.
PDB codes: 2gh0 2gyr 2gyz
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.