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PDBsum entry 1dd1

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protein ligands Protein-protein interface(s) links
Signaling protein PDB id
1dd1
Jmol
Contents
Protein chains
221 a.a. *
249 a.a. *
Ligands
SO4 ×9
Waters ×302
* Residue conservation analysis
PDB id:
1dd1
Name: Signaling protein
Title: Crystal structure analysis of the smad4 active fragment
Structure: Smad4. Chain: a, b, c. Fragment: smad4 active fragment
Source: Homo sapiens. Human. Organism_taxid: 9606
Biol. unit: Trimer (from PQS)
Resolution:
2.62Å     R-factor:   0.218     R-free:   0.175
Authors: B.Y.Qin,S.W.Lam,K.Lin
Key ref:
B.Qin et al. (1999). Crystal structure of a transcriptionally active Smad4 fragment. Structure, 7, 1493-1503. PubMed id: 10647180 DOI: 10.1016/S0969-2126(00)88340-9
Date:
05-Nov-99     Release date:   27-Nov-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q13485  (SMAD4_HUMAN) -  Mothers against decapentaplegic homolog 4
Seq:
Struc:
 
Seq:
Struc:
552 a.a.
221 a.a.
Protein chains
Pfam   ArchSchema ?
Q13485  (SMAD4_HUMAN) -  Mothers against decapentaplegic homolog 4
Seq:
Struc:
 
Seq:
Struc:
552 a.a.
249 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 

 

 
DOI no: 10.1016/S0969-2126(00)88340-9 Structure 7:1493-1503 (1999)
PubMed id: 10647180  
 
 
Crystal structure of a transcriptionally active Smad4 fragment.
B.Qin, S.S.Lam, K.Lin.
 
  ABSTRACT  
 
BACKGROUND: Smad4 functions as a common mediator of transforming growth factor beta (TGF-beta) signaling by forming complexes with the phosphorylated state of pathway-restricted SMAD proteins that act in specific signaling pathways to activate transcription. SMAD proteins comprise two domains, the MH1 and MH2 domain, separated by a linker region. The transcriptional activity and synergistic effect of Smad4 require a stretch of proline-rich sequence, the SMAD-activation domain (SAD), located N-terminal of the MH2 domain. To understand how the SAD contributes to Smad4 function, the crystal structure of a fragment including the SAD and MH2 domain (S4AF) was determined. RESULTS: The structure of the S4AF trimer reveals novel features important for Smad4 function. A Smad4-specific sequence insertion within the MH2 domain interacts with the C-terminal tail to form a structural extension from the core. This extension (the TOWER) contains a solvent-accessible glutamine-rich helix. The SAD reinforces the TOWER and the structural core through interactions; two residues involved in these interactions are targets of tumorigenic mutation. The solvent-accessible proline residues of the SAD are located on the same face as the glutamine-rich helix of the TOWER, forming a potential transcription activation surface. A tandem sulfate-ion-binding site was identified within the subunit interface, which may interact with the phosphorylated C-terminal sequence of pathway-restricted SMAD proteins. CONCLUSIONS: The structure suggests that the SAD provides transcriptional capability by reinforcing the structural core and coordinating with the TOWER to present the proline-rich and glutamine-rich surfaces for interaction with transcription partners. The sulfate-ion-binding sites are potential 'receptors' for the phosphorylated sequence of pathway-restricted SMAD proteins in forming a heteromeric complex. The structure thus provides a new model that can be tested using biochemical and cellular approaches.
 
  Selected figure(s)  
 
Figure 9.
Figure 9. Proposed model of the heteromeric interaction between Smad4 and pathway-restricted SMAD proteins. The phosphorylated C-terminal tail sequence (in ball-and-stick format) of the pathway-restricted SMAD protein adopts an extended conformation to reach the interface between two Smad4 subunits. The three monomers are shown in different colors.
 
  The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 1493-1503) copyright 1999.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19557331 C.Wang, L.Chen, L.Wang, and J.Wu (2009).
Crystal structure of the MH2 domain of Drosophila Mad.
  Sci China C Life Sci, 52, 539-544.
PDB code: 3gmj
17140726 T.F.Lerch, M.Xu, T.S.Jardetzky, K.E.Mayo, I.Radhakrishnan, R.Kazer, L.D.Shea, and T.K.Woodruff (2007).
The structures that underlie normal reproductive function.
  Mol Cell Endocrinol, 267, 1-5.  
17959720 Y.Saka, A.I.Hagemann, O.Piepenburg, and J.C.Smith (2007).
Nuclear accumulation of Smad complexes occurs only after the midblastula transition in Xenopus.
  Development, 134, 4209-4218.  
16433931 H.T.Chang, T.W.Pai, T.C.Fan, B.H.Su, P.C.Wu, C.Y.Tang, C.T.Chang, S.H.Liu, and M.D.Chang (2006).
A reinforced merging methodology for mapping unique peptide motifs in members of protein families.
  BMC Bioinformatics, 7, 38.  
14630909 A.Osman, E.G.Niles, and P.T.LoVerde (2004).
Expression of functional Schistosoma mansoni Smad4: role in Erk-mediated transforming growth factor beta (TGF-beta) down-regulation.
  J Biol Chem, 279, 6474-6486.  
14729957 R.A.Randall, M.Howell, C.S.Page, A.Daly, P.A.Bates, and C.S.Hill (2004).
Recognition of phosphorylated-Smad2-containing complexes by a novel Smad interaction motif.
  Mol Cell Biol, 24, 1106-1121.  
14500786 G.I.Lee, Z.Ding, J.C.Walker, and S.R.Van Doren (2003).
NMR structure of the forkhead-associated domain from the Arabidopsis receptor kinase-associated protein phosphatase.
  Proc Natl Acad Sci U S A, 100, 11261-11266.
PDB codes: 1mzk 1n4t
14555995 K.Takahasi, N.N.Suzuki, M.Horiuchi, M.Mori, W.Suhara, Y.Okabe, Y.Fukuhara, H.Terasawa, S.Akira, T.Fujita, and F.Inagaki (2003).
X-ray crystal structure of IRF-3 and its functional implications.
  Nat Struct Biol, 10, 922-927.
PDB code: 1j2f
12917407 L.Xu, C.Alarcón, S.Cöl, and J.Massagué (2003).
Distinct domain utilization by Smad3 and Smad4 for nucleoporin interaction and nuclear import.
  J Biol Chem, 278, 42569-42577.  
12440701 A.Mehra, and J.L.Wrana (2002).
TGF-beta and the Smad signal transduction pathway.
  Biochem Cell Biol, 80, 605-622.  
12154125 B.Y.Qin, S.S.Lam, J.J.Correia, and K.Lin (2002).
Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control.
  Genes Dev, 16, 1950-1963.
PDB codes: 1mjs 1mk2
11818142 D.U.Kloos, C.Choi, and E.Wingender (2002).
The TGF-beta--Smad network: introducing bioinformatic tools.
  Trends Genet, 18, 96.  
12374795 G.J.Inman, and C.S.Hill (2002).
Stoichiometry of active smad-transcription factor complexes on DNA.
  J Biol Chem, 277, 51008-51016.  
  11294908 A.Kurisaki, S.Kose, Y.Yoneda, C.H.Heldin, and A.Moustakas (2001).
Transforming growth factor-beta induces nuclear import of Smad3 in an importin-beta1 and Ran-dependent manner.
  Mol Biol Cell, 12, 1079-1091.  
11779505 B.Y.Qin, B.M.Chacko, S.S.Lam, M.P.de Caestecker, J.J.Correia, and K.Lin (2001).
Structural basis of Smad1 activation by receptor kinase phosphorylation.
  Mol Cell, 8, 1303-1312.
PDB code: 1khu
11553622 D.Maurice, C.E.Pierreux, M.Howell, R.E.Wilentz, M.J.Owen, and C.S.Hill (2001).
Loss of Smad4 function in pancreatic tumors: C-terminal truncation leads to decreased stability.
  J Biol Chem, 276, 43175-43181.  
11779503 J.W.Wu, M.Hu, J.Chai, J.Seoane, M.Huse, C.Li, D.J.Rigotti, S.Kyin, T.W.Muir, R.Fairman, J.Massagué, and Y.Shi (2001).
Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.
  Mol Cell, 8, 1277-1289.
PDB code: 1khx
  11532220 L.Attisano, and S.Tuen Lee-Hoeflich (2001).
The Smads.
  Genome Biol, 2, REVIEWS3010.  
11223879 Y.Shi (2001).
Structural insights on Smad function in TGFbeta signaling.
  Bioessays, 23, 223-232.  
11160896 Z.A.Quinn, C.C.Yang, J.L.Wrana, and J.C.McDermott (2001).
Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins.
  Nucleic Acids Res, 29, 732-742.  
10636916 M.P.de Caestecker, T.Yahata, D.Wang, W.T.Parks, S.Huang, C.S.Hill, T.Shioda, A.B.Roberts, and R.J.Lechleider (2000).
The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain.
  J Biol Chem, 275, 2115-2122.  
  10887155 R.H.Kim, D.Wang, M.Tsang, J.Martin, C.Huff, M.P.de Caestecker, W.T.Parks, X.Meng, R.J.Lechleider, T.Wang, and A.B.Roberts (2000).
A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction.
  Genes Dev, 14, 1605-1616.  
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.