PDBsum entry 1m1e

Structural protein

PDB id: 1m1e

Contents

Protein chains

512 a.a. *

65 a.a. *

Waters ×310

* Residue conservation analysis

PDB id:

1m1e

Name:

Structural protein

Title:

Beta-catenin armadillo repeat domain bound to icat

Structure:

Beta-catenin. Chain: a. Fragment: armadillo repeat region (residues 134-671). Engineered: yes. Icat. Chain: b. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21.

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.202 R-free: 0.228

Authors:

D.L.Daniels,W.I.Weis

Key ref:

D.L.Daniels and W.I.Weis (2002). ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules. Mol Cell, 10, 573-584. PubMed id: 12408825 DOI: 10.1016/S1097-2765(02)00631-7

Date:

18-Jun-02 Release date: 16-Oct-02

Protein chain

Q02248  (CTNB1_MOUSE) -  Catenin beta-1 from Mus musculus

Seq: 781 a.a.

Struc: 512 a.a.

Protein chain

Q9NSA3  (CNBP1_HUMAN) -  Beta-catenin-interacting protein 1 from Homo sapiens

Seq: 81 a.a.

Struc: 65 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1016/S1097-2765(02)00631-7

Mol Cell 10:573-584 (2002)

PubMed id: 12408825

ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.

D.L.Daniels, W.I.Weis.

ABSTRACT

In the canonical Wnt signaling pathway, beta-catenin activates target genes through its interactions with Tcf/Lef-family transcription factors and additional transcriptional coactivators. The crystal structure of ICAT, an inhibitor of beta-catenin-mediated transcription, bound to the armadillo repeat domain of beta-catenin, has been determined. ICAT contains an N-terminal helilical domain that binds to repeats 11 and 12 of beta-catenin, and an extended C-terminal region that binds to repeats 5-10 in a manner similar to that of Tcfs and other beta-catenin ligands. Full-length ICAT dissociates complexes of beta-catenin, Lef-1, and the transcriptional coactivator p300, whereas the helical domain alone selectively blocks binding to p300. The C-terminal armadillo repeats of beta-catenin may be an attractive target for compounds designed to disrupt aberrant beta-catenin-mediated transcription associated with various cancers.

Selected figure(s)

Figure 2.
Figure 2. The ICAT Helical Domain(A) Structure of the helical domain showing key hydrophobic core packing interactions. Helices A, B, and C are indicated.(B) Hydrophobic interactions between helix A and residues of β-catenin. The color scheme is the same as Figure 1B, with β-catenin arm repeats 11 and 12 termed R11 and R12, respectively. Side chains from each protein that participate in hydrophobic interactions are shown. Also shown is the superposition of the region II helix of E-cadherin (Huber and Weis, 2001) (yellow; residue numbers shown in parentheses). The superposition was performed as described in Figure 1C. The hydrogen bond between Tyr 654 of β-catenin and Asp 665 of E-cadherin is shown with a solid line.(C) Electrostatic interactions (dashed lines) of ICAT glutamate residues 37, 38, and 39 with arginine residues in β-catenin or within ICAT, labeled as in (B). Mutation of these three residues to alanine abolishes ICAT binding to β-catenin.

Figure 5.
Figure 5. Model of ICAT as a Bipartite Transcriptional InhibitorOn the left, transcription activation complexes consisting of β-catenin, Tcf/Lef, and CBP/p300 are bound to cognate DNA sites through interaction of the Tcf/Lef HMG box. Binding of ICAT to β-catenin simultaneously displaces CBP/p300 and Tcf/Lef, allowing for Groucho/TLE repressor proteins to bind to Tcf/Lef.

The above figures are reprinted by permission from Cell Press: Mol Cell (2002, 10, 573-584) copyright 2002.

Figures were selected by an automated process.