Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68

Structure. 2011 Oct 12;19(10):1496-508. doi: 10.1016/j.str.2011.07.013.


Adenomatous polyposis coli (APC) is a tumor suppressor protein commonly mutated in colorectal tumors. APC plays important roles in Wnt signaling and other cellular processes. Here, we present the crystal structure of the armadillo repeat (Arm) domain of APC, which facilitates the binding of APC to various proteins. APC-Arm forms a superhelix with a positively charged groove. We also determined the structure of the complex of APC-Arm with the tyrosine-rich (YY) domain of the Src-associated in mitosis, 68 kDa protein (Sam68), which regulates TCF-1 alternative splicing. Sam68-YY forms numerous interactions with the residues on the groove and is thereby fixed in a bent conformation. We assessed the effects of mutations and phosphorylation on complex formation between APC-Arm and Sam68-YY. Structural comparisons revealed different modes of ligand recognition between the Arm domains of APC and other Arm-containing proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adenomatous Polyposis Coli Protein / chemistry*
  • Alternative Splicing
  • Cloning, Molecular
  • Computer Simulation
  • DNA-Binding Proteins / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Humans
  • Multiprotein Complexes / chemistry*
  • Mutation, Missense
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • RNA-Binding Proteins / chemistry*
  • Selenomethionine / chemistry
  • X-Ray Diffraction


  • APC protein, human
  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein
  • DNA-Binding Proteins
  • KHDRBS1 protein, human
  • Multiprotein Complexes
  • RNA-Binding Proteins
  • Selenomethionine

Associated data

  • PDB/3AU3
  • PDB/3QHE