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PDBsum entry 2djy

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protein Protein-protein interface(s) links
Ligase/signaling protein PDB id
2djy
Jmol
Contents
Protein chains
42 a.a. *
20 a.a. *
* Residue conservation analysis
PDB id:
2djy
Name: Ligase/signaling protein
Title: Solution structure of smurf2 ww3 domain-smad7 py peptide complex
Structure: Smad ubiquitination regulatory factor 2. Chain: a. Fragment: ww3 domain. Synonym: ubiquitin--protein ligase smurf2, smad-specific e3 ubiquitin ligase 2, hsmurf2. Engineered: yes. Mothers against decapentaplegic homolog 7. Chain: b. Fragment: py motif region.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: smurf2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: smad7, madh7, madh8.
NMR struc: 30 models
Authors: P.A.Chong,H Lin,J.L.Wrana,J.D.Forman-Kay
Key ref:
P.A.Chong et al. (2006). An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2. J Biol Chem, 281, 17069-17075. PubMed id: 16641086 DOI: 10.1074/jbc.M601493200
Date:
06-Apr-06     Release date:   02-May-06    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9HAU4  (SMUF2_HUMAN) -  E3 ubiquitin-protein ligase SMURF2
Seq:
Struc:
 
Seq:
Struc:
748 a.a.
42 a.a.*
Protein chain
Pfam   ArchSchema ?
O15105  (SMAD7_HUMAN) -  Mothers against decapentaplegic homolog 7
Seq:
Struc:
426 a.a.
20 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 

 
DOI no: 10.1074/jbc.M601493200 J Biol Chem 281:17069-17075 (2006)
PubMed id: 16641086  
 
 
An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2.
P.A.Chong, H.Lin, J.L.Wrana, J.D.Forman-Kay.
 
  ABSTRACT  
 
Smurf2 is an E3 ubiquitin ligase that drives degradation of the transforming growth factor-beta receptors and other targets. Recognition of the receptors by Smurf2 is accomplished through an intermediary protein, Smad7. Here we have demonstrated that the WW3 domain of Smurf2 can directly bind to the Smad7 polyproline-tyrosine (PY) motif. Of particular interest, the highly conserved WW domain binding site Trp, which interacts with target PY motifs, is a Phe in the Smurf2 WW3 domain. To examine this interaction, the solution structure of the complex between the Smad7 PY motif region (ELESPPPPYSRYPMD) and the Smurf2 WW3 domain was determined. The structure reveals that, in addition to binding the PY motif, the WW3 domain binds six residues C-terminal to the PY motif (PY-tail). Although the Phe in the WW3 domain binding site decreases affinity relative to the canonical Trp, this is balanced by additional interactions between the PY-tail and the beta1-strand and beta1-beta2 loop of the WW3 domain. The interaction between the Smurf2 WW3 domain and the Smad7 PY motif is the first example of PY motif recognition by a WW domain with a Phe substituted for the binding site Trp. This unusual interaction allows the Smurf2 WW3 domain to recognize a subset of PY motif-containing proteins utilizing an expanded surface to provide specificity.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. Solution structure of the Smurf2 WW3 domain-Smad7 PY peptide complex. a, superposition of the 30 lowest energy structures. The WW3 domain backbone is shown in blue and side chains in turquoise, except for positions typically occupied by conserved Trp residues, which are in green. The PY peptide backbone is red with side chains shown in gold. b, ribbon diagram of the lowest energy structure. The coloring scheme is as in a, except that WW3 domain loop regions are shown in gray. Residues designated with a prime symbol (') are Smad7 residues. For clarity, some side chains are not shown. Figs. 1, 2, 3a, and 5b were generated using MOLMOL (37). N, N terminus; C, C terminus.
Figure 2.
FIGURE 2. Superposition of the PY motifs and binding pockets from the Smad7-Smurf2 WW3 domain complex and the -dystroglycan-dystrophin WW domain complex. Smad7 and Smurf2 are shown in red and blue and -dystroglycan and dystrophin in black and gray, respectively. Labels in parentheses indicate residues from the -dystroglycan-dystrophin complex.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 17069-17075) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20937913 P.A.Chong, H.Lin, J.L.Wrana, and J.D.Forman-Kay (2010).
Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity.
  Proc Natl Acad Sci U S A, 107, 18404-18409.
PDB code: 2kxq
19937093 S.Li, K.Lu, J.Wang, L.An, G.Yang, H.Chen, Y.Cui, X.Yin, P.Xie, G.Xing, F.He, and L.Zhang (2010).
Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation.
  Mol Cell Biochem, 338, 11-17.  
19855015 P.Kahlem, and S.J.Newfeld (2009).
Informatics approaches to understanding TGFbeta pathway regulation.
  Development, 136, 3729-3740.  
18061509 S.Ross, and C.S.Hill (2008).
How the Smads regulate transcription.
  Int J Biochem Cell Biol, 40, 383-408.  
17437719 B.Morales, X.Ramirez-Espain, A.Z.Shaw, P.Martin-Malpartida, F.Yraola, E.Sánchez-Tilló, C.Farrera, A.Celada, M.Royo, and M.J.Macias (2007).
NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30 inhibits the interaction with PPxY-containing ligands.
  Structure, 15, 473-483.
PDB codes: 2jo9 2joc
17502622 J.D.Kulman, J.E.Harris, L.Xie, and E.W.Davie (2007).
Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that binds to the transcriptional coactivator Yes-associated protein.
  Proc Natl Acad Sci U S A, 104, 8767-8772.  
17686488 M.Meiyappan, G.Birrane, and J.A.Ladias (2007).
Structural basis for polyproline recognition by the FE65 WW domain.
  J Mol Biol, 372, 970-980.
PDB codes: 2ho2 2idh 2oei
17719543 S.Wiesner, A.A.Ogunjimi, H.R.Wang, D.Rotin, F.Sicheri, J.L.Wrana, and J.D.Forman-Kay (2007).
Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain.
  Cell, 130, 651-662.
PDB code: 2jqz
16925950 L.Izzi, and L.Attisano (2006).
Ubiquitin-dependent regulation of TGFbeta signaling in cancer.
  Neoplasia, 8, 677-688.  
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.