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PDBsum entry 3evs
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protein Protein-protein interface(s) links
Cytokine/transferase receptor PDB id
3evs

 

 

 

 

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Contents
Protein chains
104 a.a. *
85 a.a. *
Waters ×51
* Residue conservation analysis
PDB id:
3evs
Name: Cytokine/transferase receptor
Title: Crystal structure of the gdf-5:bmp receptor ib complex.
Structure: Growth/differentiation factor 5. Chain: b. Fragment: unp residues 387-501. Synonym: gdf-5, cartilage-derived morphogenetic protein 1, cdmp-1, radotermin. Engineered: yes. Bone morphogenetic protein receptor type-1b. Chain: c. Fragment: extracellular domain.
Source: Homo sapiens. Human. Organism_taxid: 9606. Strain: u2os. Gene: cdmp1, gdf5. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. Mouse.
Resolution:
2.10Å     R-factor:   0.217     R-free:   0.256
Authors: A.Kotzsch,T.D.Mueller
Key ref: A.Kotzsch et al. (2009). Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity. Embo J, 28, 937-947. PubMed id: 19229295
Date:
13-Oct-08     Release date:   10-Mar-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P43026  (GDF5_HUMAN) -  Growth/differentiation factor 5 from Homo sapiens
Seq:
Struc: 		501 a.a.
104 a.a.
Protein chain
Pfam   ArchSchema ?
P36898  (BMR1B_MOUSE) -  Bone morphogenetic protein receptor type-1B from Mus musculus
Seq:
Struc: 		502 a.a.
85 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain C: E.C.2.7.11.30  - receptor protein serine/threonine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor- protein] + ADP + H+
2. L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor- protein] + ADP + H+
L-seryl-[receptor-protein]
 + ATP
 = O-phospho-L-seryl-[receptor- protein]
 + ADP
 + H(+)
L-threonyl-[receptor-protein]
 + ATP
 = O-phospho-L-threonyl-[receptor- protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Embo J 28:937-947 (2009)
PubMed id: 19229295  
 
 
Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity.
A.Kotzsch, J.Nickel, A.Seher, W.Sebald, T.D.Müller.
 
  ABSTRACT  
 
Dysregulation of growth and differentiation factor 5 (GDF-5) signalling, a member of the TGF-beta superfamily, is strongly linked to skeletal malformation. GDF-5-mediated signal transduction involves both BMP type I receptors, BMPR-IA and BMPR-IB. However, mutations in either GDF-5 or BMPR-IB lead to similar phenotypes, indicating that in chondrogenesis GDF-5 signalling seems to be exclusively mediated through BMPR-IB. Here, we present structural insights into the GDF-5:BMPR-IB complex revealing how binding specificity for BMPR-IB is generated on a molecular level. In BMPR-IB, a loop within the ligand-binding epitope functions similar to a latch allowing high-affinity binding of GDF-5. In BMPR-IA, this latch is in a closed conformation leading to steric repulsion. The new structural data now provide also a molecular basis of how phenotypically relevant missense mutations in GDF-5 might impair receptor binding and activation.
 

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.  
20667411 O.F.Zouani, C.Chollet, B.Guillotin, and M.C.Durrieu (2010).
Differentiation of pre-osteoblast cells on poly(ethylene terephthalate) grafted with RGD and/or BMPs mimetic peptides.
  Biomaterials, 31, 8245-8253.  
  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
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.  
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.  
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.

 

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