Crystal structure of the amino-terminal coiled-coil domain of the APC tumor suppressor

J Mol Biol. 2000 Aug 4;301(1):147-56. doi: 10.1006/jmbi.2000.3895.


Coiled coils serve as dimerization domains for a wide variety of proteins, including the medically important oligomeric tumor suppressor protein, APC. Mutations in the APC gene are associated with an inherited susceptibility to colon cancer and with approximately 75 % of sporadic colorectal tumors. To define the basis for APC pairing and to explore the anatomy of dimeric coiled coils, we determined the 2.4 A resolution X-ray crystal structure of the N-terminal dimerization domain of APC. The peptide APC-55, encompassing the heptad repeats in APC residues 2-55, primarily forms an alpha-helical, coiled-coil dimer with newly observed core packing features. Correlated asymmetric packing of four core residues in distinct, standard rotamers is associated with a small shift in the helix register. At the C terminus, the helices splay apart and interact with a symmetry-related dimer in the crystal to form a short, anti-parallel, four-helix bundle. N-terminal fraying and C-terminal splaying of the helices, as well as the asymmetry and helix register shift describe unprecedented dynamic excursions of coiled coils. The low stability of APC-55 and divergence from the expected coiled-coil fold support the suggestion that the APC dimerization domain may extend beyond the first 55 residues.

Publication types

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

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins*
  • Dimerization
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • Genes, Tumor Suppressor
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins*


  • Adenomatous Polyposis Coli Protein
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • Neoplasm Proteins
  • Peptide Fragments
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases

Associated data

  • PDB/1DEB