PDBsum entry: 1g3j

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PDB-id

1g3j


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Protein chains

Waters ×263

* Residue conservation analysis

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PDB id:

1g3j

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Transcription

Title:

Crystal structure of the xtcf3-cbd/beta-catenin armadillo repeat complex

Structure:

Beta-catenin armadillo repeat region. Chain: a, c. Engineered: yes. Tcf3-cbd (catenin binding domain). Chain: b, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Xenopus laevis. African clawed frog. Organism_taxid: 8355. Expression_system_taxid: 562

Biological unit:

Dimer (from PQS)

UniProt:

Chain A: P35222 (CTNB1_HUMAN)

Seq:

Struc:


Seq:

Struc:


Seq:

Struc:


Seq:				781 a.a.

Struc:				522 a.a.

Chain B: P70062 (T7L1A_XENLA)

Seq:

Struc:


Seq:

Struc:


Seq:				554 a.a.

Struc:				41 a.a.

Chain C: P35222 (CTNB1_HUMAN)

Seq:

Struc:


Seq:

Struc:


Seq:

Struc:


Seq:				781 a.a.

Struc:				439 a.a.

Chain D: P70062 (T7L1A_XENLA)

Seq:

Struc:

Seq:

Struc:

Seq:

554 a.a.

Struc:

34 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Resolution:

2.10Å

R-factor:

0.229

R-free:

0.255

Authors:

T.A.Graham,C.Weaver,F.Mao,D.Kimelman,W.Xu

Key ref:

T.A.Graham et al. (2000). Crystal structure of a beta-catenin/Tcf complex.. Cell, 103, 885-896. [PubMed id: 11136974] [DOI: 10.1016/S0092-8674(00)00192-6]

Date:

24-Oct-00

Release date:

11-Dec-00

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Key reference

DOI no: 10.1016/S0092-8674(00)00192-6 Cell 103:885-896 (2000)

PubMed id: 11136974

Crystal structure of a beta-catenin/Tcf complex.

T.A.Graham, C.Weaver, F.Mao, D.Kimelman, W.Xu.

ABSTRACT

The Wnt signaling pathway plays critical roles in embryonic development and tumorigenesis. Stimulation of the Wnt pathway results in the accumulation of a nuclear beta-catenin/Tcf complex, activating Wnt target genes. A crystal structure of beta-catenin bound to the beta-catenin binding domain of Tcf3 (Tcf3-CBD) has been determined. The Tcf3-CBD forms an elongated structure with three binding modules that runs antiparallel to beta-catenin along the positively charged groove formed by the armadillo repeats. Structure-based mutagenesis defines three sites in beta-catenin that are critical for binding the Tcf3-CBD and are differentially involved in binding APC, cadherin, and Axin. The structural and mutagenesis data reveal a potential target for molecular drug design studies.

Selected figure(s)

Figure 3.
Figure 3. The Interactions between β-Catenin and the β Strand in the Extended Region of XTcf3-CBD(A) Stereo 2F[o]−F[c] simulated annealed omit map of XTcf3-CBD. XTcf3 residues are denoted in yellow and β-catenin residues are denoted in red. Solvent molecules are shown in turquoise. The map is shown at a level of 1σ.(B) Structure of the XTcf3 extended region on the top of the β-catenin molecular surface. Two semi-buried charged buttons, Lys-435 and Lys-312, are critical for the β-catenin/Tcf interactions. The β-catenin surface was cut off in the upper part of the figure to be able to view the extended region of XTcf3-CBD. XTcf3 residues are shown in white and exposed β-catenin residues due to the cut surface are shown in green. XTcf3 residues are labeled in yellow and β-catenin residues are labeled in white. The equipotential contours at the relative levels of 10, 20, 30, 40, and 50 were calculated with GRASP and are shown in white.(C) XTcf3 extended region bonding diagram. The same conventions are used as in Figure 2B. Figure 4.
Figure 4. The Interactions between β-Catenin and the XTcf3-CBD Helix(A) Molecular model of the XTcf3 helical region. XTcf3 residues are labeled in yellow and β-catenin residues are labeled in white.(B) XTcf3 helix module bonding diagram. The same conventions are used as in Figure 2B.

The above figures are reprinted by permission from Cell Press: Cell (2000, 103, 885-896) copyright 2000.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

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.

19513107 E.Zeqiraj, B.M.Filippi, S.Goldie, I.Navratilova, J.Boudeau, M.Deak, D.R.Alessi, and D.M.van Aalten (2009).
ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor.

PLoS Biol, 7, e1000126.

PDB code: 3gni

20066091 K.M.Cadigan, and M.Peifer (2009).
Wnt signaling from development to disease: insights from model systems.

Cold Spring Harbor Perspect Biol, 1, a002881.

19924301 M.E.Beildeck, M.Islam, S.Shah, J.Welsh, and S.W.Byers (2009).
Control of TCF-4 expression by VDR and vitamin D in the mouse mammary gland and colorectal cancer cell lines.

PLoS One, 4, e7872.

19365405 S.L.Lai, A.J.Chien, and R.T.Moon (2009).
Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis.

Cell Res, 19, 532-545.

19277525 Y.Shi (2009).
Assembly and structure of protein phosphatase 2A.

Sci China C Life Sci, 52, 135-146.

18432252 A.Klaus, and W.Birchmeier (2008).
Wnt signalling and its impact on development and cancer.

Nat Rev Cancer, 8, 387-398.

18682750 I.M.Somorjai, and A.Martinez-Arias (2008).
Wingless signalling alters the levels, subcellular distribution and dynamics of Armadillo and E-cadherin in third instar larval wing imaginal discs.

PLoS ONE, 3, e2893.

18193033 J.Li, and C.Y.Wang (2008).
TBL1-TBLR1 and beta-catenin recruit each other to Wnt target-gene promoter for transcription activation and oncogenesis.

Nat Cell Biol, 10, 160-169.

18086858 S.Bahmanyar, D.D.Kaplan, J.G.Deluca, T.H.Giddings, E.T.O'Toole, M.Winey, E.D.Salmon, P.J.Casey, W.J.Nelson, and A.I.Barth (2008).
beta-Catenin is a Nek2 substrate involved in centrosome separation.

Genes Dev, 22, 91.

18451518 S.Yamakawa, A.Demizu, Y.Kawaratani, Y.Nagaoka, Y.Terada, S.Maruyama, and S.Uesato (2008).
Growth inhibition of human colon cancer cell line HCT116 by bis[2-(acylamino)phenyl] disulfide and its action mechanism.

Biol Pharm Bull, 31, 916-920.

18573080 V.N.Uversky, C.J.Oldfield, and A.K.Dunker (2008).
Intrinsically disordered proteins in human diseases: introducing the D2 concept.

Annu Rev Biophys, 37, 215-246.

17620598 H.Tidow, R.Melero, E.Mylonas, S.M.Freund, J.G.Grossmann, J.M.Carazo, D.I.Svergun, M.Valle, and A.R.Fersht (2007).
Quaternary structures of tumor suppressor p53 and a specific p53 DNA complex.

Proc Natl Acad Sci U S A, 104, 12324-12329.

17009320 J.P.Muñoz, C.H.Huichalaf, D.Orellana, and R.B.Maccioni (2007).
cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal cells.

J Cell Biochem, 100, 738-749.

17660262 M.Ritco-Vonsovici, A.Ababou, and M.Horton (2007).
Molecular plasticity of beta-catenin: new insights from single-molecule measurements and MD simulation.

Protein Sci, 16, 1984-1998.

17000761 A.Schepsky, K.Bruser, G.J.Gunnarsson, J.Goodall, J.H.Hallsson, C.R.Goding, E.Steingrimsson, and A.Hecht (2006).
The microphthalmia-associated transcription factor Mitf interacts with beta-catenin to determine target gene expression.

Mol Cell Biol, 26, 8914-8927.

17143292 D.Kimelman, and W.Xu (2006).
beta-catenin destruction complex: insights and questions from a structural perspective.

Oncogene, 25, 7482-7491.

16824055 F.Tang, Y.Peng, J.J.Nau, E.J.Kauffman, and L.S.Weisman (2006).
Vac8p, an armadillo repeat protein, coordinates vacuole inheritance with multiple vacuolar processes.

Traffic, 7, 1368-1377.

16819755 H.D.Arndt (2006).
Small molecule modulators of transcription.

Angew Chem Int Ed Engl, 45, 4552-4560.

16293619 H.J.Choi, A.H.Huber, and W.I.Weis (2006).
Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity.

J Biol Chem, 281, 1027-1038.

16847334 J.Liu, H.Wang, Y.Zuo, and S.R.Farmer (2006).
Functional interaction between peroxisome proliferator-activated receptor gamma and beta-catenin.

Mol Cell Biol, 26, 5827-5837.

16371504 J.Qi, J.Wang, O.Romanyuk, and C.H.Siu (2006).
Involvement of Src family kinases in N-cadherin phosphorylation and beta-catenin dissociation during transendothelial migration of melanoma cells.

Mol Biol Cell, 17, 1261-1272.

16568448 J.Y.Trosset, C.Dalvit, S.Knapp, M.Fasolini, M.Veronesi, S.Mantegani, L.M.Gianellini, C.Catana, M.Sundström, P.F.Stouten, and J.K.Moll (2006).
Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening.

Proteins, 64, 60-67.

17143293 L.Arce, N.N.Yokoyama, and M.L.Waterman (2006).
Diversity of LEF/TCF action in development and disease.

Oncogene, 25, 7492-7504.

17139285 N.Barker, and H.Clevers (2006).
Mining the Wnt pathway for cancer therapeutics.

Nat Rev Drug Discov, 5, 997.

16683072 N.Janssens, M.Janicot, and T.Perera (2006).
The Wnt-dependent signaling pathways as target in oncology drug discovery.

Invest New Drugs, 24, 263-280.

16283145 D.C.Fry, and L.T.Vassilev (2005).
Targeting protein-protein interactions for cancer therapy.

J Mol Med, 83, 955-963.

15768032 D.L.Daniels, and W.I.Weis (2005).
Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation.

Nat Struct Mol Biol, 12, 364-371.

15738986 H.J.Dyson, and P.E.Wright (2005).
Intrinsically unstructured proteins and their functions.

Nat Rev Mol Cell Biol, 6, 197-208.

16231302 J.Perry (2005).
Weighing in on a Timeless controversy.

Proteins, 61, 699-703.

16141201 L.N.Song, and E.P.Gelmann (2005).
Interaction of beta-catenin and TIF2/GRIP1 in transcriptional activation by the androgen receptor.

J Biol Chem, 280, 37853-37867.

16244662 L.Opperman, B.Hook, M.DeFino, D.S.Bernstein, and M.Wickens (2005).
A single spacer nucleotide determines the specificities of two mRNA regulatory proteins.

Nat Struct Mol Biol, 12, 945-951.

16292343 M.Lammers, R.Rose, A.Scrima, and A.Wittinghofer (2005).
The regulation of mDia1 by autoinhibition and its release by Rho*GTP.

EMBO J, 24, 4176-4187.

PDB code: 2bap

15591320 R.Gail, R.Frank, and A.Wittinghofer (2005).
Systematic peptide array-based delineation of the differential beta-catenin interaction with Tcf4, E-cadherin, and adenomatous polyposis coli.

J Biol Chem, 280, 7107-7117.

15472907 S.Dihlmann, and M.von Knebel Doeberitz (2005).
Wnt/beta-catenin-pathway as a molecular target for future anti-cancer therapeutics.

Int J Cancer, 113, 515-524.

14730349 C.C.Milburn, J.Boudeau, M.Deak, D.R.Alessi, and D.M.van Aalten (2004).
Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor.

Nat Struct Mol Biol, 11, 193-200.

PDB codes: 1upk 1upl

15492040 C.J.Gottardi, and B.M.Gumbiner (2004).
Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes.

J Cell Biol, 167, 339-349.

15381698 G.Solanas, S.Miravet, D.Casagolda, J.Castaño, I.Raurell, A.Corrionero, A.G.de Herreros, and M.Duñach (2004).
beta-Catenin and plakoglobin N- and C-tails determine ligand specificity.

J Biol Chem, 279, 49849-49856.

15112230 J.M.Gooding, K.L.Yap, and M.Ikura (2004).
The cadherin-catenin complex as a focal point of cell adhesion and signalling: new insights from three-dimensional structures.

Bioessays, 26, 497-511.

15314234 K.H.Emami, C.Nguyen, H.Ma, D.H.Kim, K.W.Jeong, M.Eguchi, R.T.Moon, J.L.Teo, S.W.Oh, H.Y.Kim, S.H.Moon, J.R.Ha, and M.Kahn (2004).
A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected].

Proc Natl Acad Sci U S A, 101, 12682-12687.

15060161 L.Lévy, Y.Wei, C.Labalette, Y.Wu, C.A.Renard, M.A.Buendia, and C.Neuveut (2004).
Acetylation of beta-catenin by p300 regulates beta-catenin-Tcf4 interaction.

Mol Cell Biol, 24, 3404-3414.

14991001 L.Xu, and J.Massagué (2004).
Nucleocytoplasmic shuttling of signal transducers.

Nat Rev Mol Cell Biol, 5, 209-219.

15024404 N.S.Tolwinski, and E.Wieschaus (2004).
A nuclear function for armadillo/beta-catenin.

PLoS Biol, 2, E95.

12446687 A.Hecht, and M.P.Stemmler (2003).
Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4.

J Biol Chem, 278, 3776-3785.

12799378 A.L.Amir, M.Barua, N.C.McKnight, S.Cheng, X.Yuan, and S.P.Balk (2003).
A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4.

J Biol Chem, 278, 30828-30834.

12700239 D.H.Song, I.Dominguez, J.Mizuno, M.Kaut, S.C.Mohr, and D.C.Seldin (2003).
CK2 phosphorylation of the armadillo repeat region of beta-catenin potentiates Wnt signaling.

J Biol Chem, 278, 24018-24025.

12861022 J.A.Kennell, E.E.O'Leary, B.M.Gummow, G.D.Hammer, and O.A.MacDougald (2003).
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.

Mol Cell Biol, 23, 5366-5375.

12588987 L.N.Song, R.Herrell, S.Byers, S.Shah, E.M.Wilson, and E.P.Gelmann (2003).
Beta-catenin binds to the activation function 2 region of the androgen receptor and modulates the effects of the N-terminal domain and TIF2 on ligand-dependent transcription.

Mol Cell Biol, 23, 1674-1687.

12657632 M.Fasolini, X.Wu, M.Flocco, J.Y.Trosset, U.Oppermann, and S.Knapp (2003).
Hot spots in Tcf4 for the interaction with beta-catenin.

J Biol Chem, 278, 21092-21098.

14517306 S.Miravet, J.Piedra, J.Castaño, I.Raurell, C.Francí, M.Duñach, and A.García de Herreros (2003).
Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription.

Mol Cell Biol, 23, 7391-7402.

12513953 T.J.Yeatman (2003).
The future of cancer management: translating the genome, transcriptome, and proteome.

Ann Surg Oncol, 10, 7.

12942139 T.M.Hall (2003).
SAM breaks its stereotype.

Nat Struct Biol, 10, 677-679.

12813041 W.Wang, D.Ungermannova, L.Chen, and X.Liu (2003).
A negatively charged amino acid in Skp2 is required for Skp2-Cks1 interaction and ubiquitination of p27Kip1.

J Biol Chem, 278, 32390-32396.

14600025 Y.Xing, W.K.Clements, D.Kimelman, and W.Xu (2003).
Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex.

Genes Dev, 17, 2753-2764.

PDB code: 1qz7

12006483 A.Hurlstone, and H.Clevers (2002).
T-cell factors: turn-ons and turn-offs.

EMBO J, 21, 2303-2311.

11880638 A.L.Simon, E.A.Stone, and A.Sidow (2002).
Inference of functional regions in proteins by quantification of evolutionary constraints.

Proc Natl Acad Sci U S A, 99, 2912-2917.

11821382 D.Gradl, A.König, and D.Wedlich (2002).
Functional diversity of Xenopus lymphoid enhancer factor/T-cell factor transcription factors relies on combinations of activating and repressing elements.

J Biol Chem, 277, 14159-14171.

11792709 F.Yang, X.Li, M.Sharma, C.Y.Sasaki, D.L.Longo, B.Lim, and Z.Sun (2002).
Linking beta-catenin to androgen-signaling pathway.

J Biol Chem, 277, 11336-11344.

12135986 R.DasGupta, H.Rhee, and E.Fuchs (2002).
A developmental conundrum: a stabilized form of beta-catenin lacking the transcriptional activation domain triggers features of hair cell fate in epidermal cells and epidermal cell fate in hair follicle cells.

J Cell Biol, 158, 331-344.

11912492 T.Jimbo, Y.Kawasaki, R.Koyama, R.Sato, S.Takada, K.Haraguchi, and T.Akiyama (2002).
Identification of a link between the tumour suppressor APC and the kinesin superfamily.

Nat Cell Biol, 4, 323-327.

11533658 A.Ryo, M.Nakamura, G.Wulf, Y.C.Liou, and K.P.Lu (2001).
Pin1 regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with APC.

Nat Cell Biol, 3, 793-801.

11751639 A.V.Tutter, C.J.Fryer, and K.A.Jones (2001).
Chromatin-specific regulation of LEF-1-beta-catenin transcription activation and inhibition in vitro.

Genes Dev, 15, 3342-3354.

11524435 E.Lee, A.Salic, and M.W.Kirschner (2001).
Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon.

J Cell Biol, 154, 983-993.

11713476 F.Poy, M.Lepourcelet, R.A.Shivdasani, and M.J.Eck (2001).
Structure of a human Tcf4-beta-catenin complex.

Nat Struct Biol, 8, 1053-1057.

PDB code: 1jpw

11294915 I.Simcha, C.Kirkpatrick, E.Sadot, M.Shtutman, G.Polevoy, B.Geiger, M.Peifer, and A.Ben-Ze'ev (2001).
Cadherin sequences that inhibit beta-catenin signaling: a study in yeast and mammalian cells.

Mol Biol Cell, 12, 1177-1188.

11707392 K.Eklof Spink, S.G.Fridman, and W.I.Weis (2001).
Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex.

EMBO J, 20, 6203-6212.

PDB code: 1jpp

11713475 T.A.Graham, D.M.Ferkey, F.Mao, D.Kimelman, and W.Xu (2001).
Tcf4 can specifically recognize beta-catenin using alternative conformations.

Nat Struct Biol, 8, 1048-1052.

PDB code: 1jdh

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.