The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin

Cell. 2001 May 4;105(3):391-402. doi: 10.1016/s0092-8674(01)00330-0.

Abstract

As a component of adherens junctions and the Wnt signaling pathway, beta-catenin binds cadherins, Tcf family transcription factors, and the tumor suppressor APC. We have determined the crystal structures of both unphosphorylated and phosphorylated E-cadherin cytoplasmic domain complexed with the arm repeat region of beta-catenin. The interaction spans all 12 arm repeats, and features quasi-independent binding regions that include helices which interact with both ends of the arm repeat domain and an extended stretch of 14 residues which closely resembles a portion of XTcf-3. Phosphorylation of E-cadherin results in interactions with a hydrophobic patch of beta-catenin that mimics the binding of an amphipathic XTcf-3 helix. APC contains sequences homologous to the phosphorylated region of cadherin, and is likely to bind similarly.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Adherens Junctions / chemistry
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cadherins / chemistry*
  • Cadherins / metabolism
  • Casein Kinase II
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism
  • Desmoplakins
  • HMGB Proteins*
  • Humans
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • TCF Transcription Factors
  • Trans-Activators*
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • beta Catenin

Substances

  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • Desmoplakins
  • HMGB Proteins
  • Ligands
  • Recombinant Proteins
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Tcf7l1 protein, mouse
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
  • beta Catenin
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases