Structure of a human Tcf4-beta-catenin complex

Nat Struct Biol. 2001 Dec;8(12):1053-7. doi: 10.1038/nsb720.

Abstract

The multifunctional protein beta-catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef family transcription factors. Mutations in APC or in beta-catenin are estimated to trigger formation of over 90% of all colon cancers. In colonic epithelia, these mutations produce elevated levels of Tcf4-beta-catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4-beta-catenin interaction may be an attractive goal for therapeutic intervention. Here we describe the crystal structure of a human Tcf4-beta-catenin complex and compare it with recent structures of beta-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding Sites
  • Cadherins / chemistry
  • Cadherins / metabolism
  • Cell Line
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / antagonists & inhibitors
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism*
  • Drug Design
  • Genes, Reporter / genetics
  • HMGB Proteins*
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Repetitive Sequences, Amino Acid
  • Static Electricity
  • TCF Transcription Factors
  • Trans-Activators*
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • HMGB Proteins
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • TCF7L2 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • Xenopus Proteins
  • beta Catenin
  • tcf7l2 protein, Xenopus

Associated data

  • PDB/1JPW