PDBsum entry: 1luj

Structural protein

PDB id: 1luj

Contents

Protein chains

501 a.a. *

71 a.a. *

* Residue conservation analysis

PDB id:

1luj

Name:

Structural protein

Title:

Crystal structure of the beta-catenin/icat complex

Structure:

Beta-catenin. Chain: a. Fragment: residues 150-666. Engineered: yes. Beta-catenin-interacting protein icat. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.210 R-free: 0.255

Authors:

T.A.Graham,W.K.Clements,D.Kimelman,W.Xu

Key ref:

T.A.Graham et al. (2002). The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT. Mol Cell, 10, 563-571. PubMed id: 12408824 DOI: 10.1016/S1097-2765(02)00637-8

Date:

22-May-02 Release date: 16-Oct-02

Protein chain

P35222  (CTNB1_HUMAN) -  Catenin beta-1

Seq: 781 a.a.

Struc: 501 a.a.

Protein chain

Q9NSA3  (CNBP1_HUMAN) -  Beta-catenin-interacting protein 1

Seq: 81 a.a.

Struc: 71 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (4 terms)
• Biological process: anterior/posterior pattern formation (14 terms)
• Biochemical function: binding (4 terms)

DOI no: 10.1016/S1097-2765(02)00637-8

Mol Cell 10:563-571 (2002)

PubMed id: 12408824

The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT.

T.A.Graham, W.K.Clements, D.Kimelman, W.Xu.

ABSTRACT

Beta-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the beta-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. We have determined the crystal structure at 2.5 A resolution of a complex between beta-catenin and ICAT, a protein that prevents the interaction between beta-catenin and Tcf/Lef family transcription factors. ICAT contains a 3-helix bundle that binds armadillo repeats 10-12 and a C-terminal tail that, similar to Tcf and E-cadherin, binds in the groove formed by armadillo repeats 5-9 of beta-catenin. We show that ICAT selectively inhibits beta-catenin/Tcf binding in vivo, without disrupting beta-catenin/cadherin interactions. Thus, it should be possible to design cancer therapeutics that inhibit beta-catenin-mediated transcriptional activation without interfering with cell adhesion.

Selected figure(s)

Figure 4.
Figure 4. β-Catenin Phe660 and Arg661 Are Required for ICAT Bindingβ-catenin carrying the mutations F660A/R661A (mut βCat) was tested for its ability to bind ICAT in vitro. Wild-type (lane 1) but not mutant (lane 2) β-catenin is able to coprecipitate ICAT. All of the proteins were ^35S-labeled and mixed as described. β-catenin was immunoprecipitated via its HA-epitope tag. Lanes 4–6 show protein levels prior to immunoprecipitation.

Figure 6.
Figure 6. ICAT Selectively Blocks Tcf Binding to β-Catenin In VivoThe ability of β-catenin to bind either XTcf3-HA or C-cadherin-HA in the presence or absence of ICAT was tested in Xenopus embryos. Equivalent levels of GFP RNA were injected into embryos that did not receive ICAT RNA. Embryo lysates were immunoprecipitated (lanes 6–10) for the FLAG epitope tag on β-catenin and probed with an anti-HA antibody. Lanes 1–5 correspond to lanes 6–10 and show the levels of proteins in total lysates prior to immunoprecipitation. Lanes 1 and 6 show results from uninjected embryos. ICAT prevents coprecipitation of XTcf3 (lane 8) but not C-cad (lane 10) with β-catenin.

The above figures are reprinted by permission from Cell Press: Mol Cell (2002, 10, 563-571) copyright 2002.

Figures were selected by an automated process.