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PDBsum entry 2gl7
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protein Protein-protein interface(s) links
Transcription PDB id
2gl7

 

 

 

 

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Contents
Protein chains
512 a.a. *
30 a.a. *
23 a.a. *
28 a.a. *
17 a.a. *
Waters ×128
* Residue conservation analysis
PDB id:
2gl7
Name: Transcription
Title: Crystal structure of a beta-catenin/bcl9/tcf4 complex
Structure: Beta-catenin. Chain: a, d. Fragment: residues 138-686. Engineered: yes. Mutation: yes. Transcription factor 7-like 2. Chain: b, e. Fragment: residues 1-53. Synonym: hmg box transcription factor 4, t- cell-specific
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ctnnb1, ctnnb. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: tcf7l2, tcf4. Gene: bcl9.
Biol. unit: Trimer (from PQS)
Resolution:
2.60Å     R-factor:   0.223     R-free:   0.267
Authors: J.Sampietro
Key ref:
J.Sampietro et al. (2006). Crystal structure of a beta-catenin/BCL9/Tcf4 complex. Mol Cell, 24, 293-300. PubMed id: 17052462 DOI: 10.1016/j.molcel.2006.09.001
Date:
04-Apr-06     Release date:   31-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P35222  (CTNB1_HUMAN) -  Catenin beta-1 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		781 a.a.
512 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9NQB0  (TF7L2_HUMAN) -  Transcription factor 7-like 2 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		619 a.a.
30 a.a.
Protein chain
Pfam   ArchSchema ?
O00512  (BCL9_HUMAN) -  B-cell CLL/lymphoma 9 protein from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1426 a.a.
23 a.a.
Protein chain
Pfam   ArchSchema ?
Q9NQB0  (TF7L2_HUMAN) -  Transcription factor 7-like 2 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		619 a.a.
28 a.a.
Protein chain
Pfam   ArchSchema ?
O00512  (BCL9_HUMAN) -  B-cell CLL/lymphoma 9 protein from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1426 a.a.
17 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/j.molcel.2006.09.001 Mol Cell 24:293-300 (2006)
PubMed id: 17052462  
 
 
Crystal structure of a beta-catenin/BCL9/Tcf4 complex.
J.Sampietro, C.L.Dahlberg, U.S.Cho, T.R.Hinds, D.Kimelman, W.Xu.
 
  ABSTRACT  
 
The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A resolution. Our studies reveal that the beta-catenin binding site of BCL9 is distinct from that of most other beta-catenin partners and forms a good target for developing drugs that block canonical Wnt/beta-catenin signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix that binds to the first armadillo repeat of beta-catenin, which can be mutated to prevent beta-catenin binding to BCL9 without affecting cadherin or alpha-catenin binding. We also demonstrate that beta-catenin Y142 phosphorylation, which has been proposed to regulate BCL9-2 binding, does not directly affect the interaction of beta-catenin with either BCL9 or BCL9-2.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Point Mutations Diminish the Ability of hBcl9 to Bind to β-Catenin 		Figure 4.
Figure 4. BCL9 and BCL9-2, but Not α-Catenin, Bind Equally Well to WT β-Catenin and Y142E β-Catenin
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 24, 293-300) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20154721 E.E.Bosco, Y.Nakai, R.F.Hennigan, N.Ratner, and Y.Zheng (2010).
NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote the loss of contact inhibition of proliferation.
  Oncogene, 29, 2540-2549.  
  20182623 J.Heuberger, and W.Birchmeier (2010).
Interplay of cadherin-mediated cell adhesion and canonical Wnt signaling.
  Cold Spring Harb Perspect Biol, 2, a002915.  
20042721 M.J.Dyer, T.Akasaka, M.Capasso, P.Dusanjh, Y.F.Lee, E.L.Karran, I.Nagel, I.Vater, G.Cario, and R.Siebert (2010).
Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers?
  Blood, 115, 1490-1499.  
19412530 B.Mészáros, I.Simon, and Z.Dosztányi (2009).
Prediction of protein binding regions in disordered proteins.
  PLoS Comput Biol, 5, e1000376.  
19274088 C.L.Dahlberg, E.Z.Nguyen, D.Goodlett, and D.Kimelman (2009).
Interactions between Casein kinase Iepsilon (CKIepsilon) and two substrates from disparate signaling pathways reveal mechanisms for substrate-kinase specificity.
  PLoS ONE, 4, e4766.  
19305417 C.Mosimann, G.Hausmann, and K.Basler (2009).
Beta-catenin hits chromatin: regulation of Wnt target gene activation.
  Nat Rev Mol Cell Biol, 10, 276-286.  
19576221 S.A.Kennedy, M.L.Frazier, M.Steiniger, A.M.Mast, W.F.Marzluff, and M.R.Redinbo (2009).
Crystal structure of the HEAT domain from the Pre-mRNA processing factor Symplekin.
  J Mol Biol, 392, 115-128.
PDB code: 3gs3
18432252 A.Klaus, and W.Birchmeier (2008).
Wnt signalling and its impact on development and cancer.
  Nat Rev Cancer, 8, 387-398.  
18498752 M.Fiedler, M.J.Sánchez-Barrena, M.Nekrasov, J.Mieszczanek, V.Rybin, J.Müller, P.Evans, and M.Bienz (2008).
Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex.
  Mol Cell, 30, 507-518.
PDB codes: 2vp7 2vpb 2vpd 2vpe 2vpg
18627596 M.de la Roche, J.Worm, and M.Bienz (2008).
The function of BCL9 in Wnt/beta-catenin signaling and colorectal cancer cells.
  BMC Cancer, 8, 199.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18604449 X.Chen, J.Yang, P.M.Evans, and C.Liu (2008).
Wnt signaling: the good and the bad.
  Acta Biochim Biophys Sin (Shanghai), 40, 577-594.  
17618275 J.Rhee, T.Buchan, L.Zukerberg, J.Lilien, and J.Balsamo (2007).
Cables links Robo-bound Abl kinase to N-cadherin-bound beta-catenin to mediate Slit-induced modulation of adhesion and transcription.
  Nat Cell Biol, 9, 883-892.  
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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