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  • The EMBO Journal (2001) 20, 6203 - 6212
  • doi:10.1093/emboj/20.22.6203

Molecular mechanisms of bold beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC–bold beta-catenin complex

Katharine Eklof Spink1,2, Sofiya G. Fridman1 and William I. Weis1,2

  1. Departments of Structural Biology and of Molecular and Cellular Physiology 299 Campus Dr. West Stanford, CA 94305, USA
  2. Program in Cancer Biology, Stanford University School of Medicine, 299 Campus Dr. West Stanford, CA 94305, USA

Correspondence to:

William I. Weis, E-mail: bill.weis@stanford.edu

Received 16 August 2001; Accepted 20 September 2001; Revised 19 September 2001

The adenomatous polyposis coli (APC) tumor suppressor protein plays a critical role in regulating cellular levels of the oncogene product beta-catenin. APC binds to beta-catenin through a series of homologous 15 and 20 amino acid repeats. We have determined the crystal structure of a 15 amino acid beta-catenin binding repeat from APC bound to the armadillo repeat region of beta-catenin. Although it lacks significant sequence homology, the N-terminal half of the repeat binds in a manner similar to portions of E-cadherin and XTcf3, but the remaining interactions are unique to APC. We discuss the implications of this new structure for the design of therapeutics, and present evidence from structural, biochemical and sequence data, which suggest that the 20 amino acid repeats can adopt two modes of binding to beta-catenin.

  • Keywords:

    • adenomatous polyposis coli,
    • beta-catenin,
    • crystal structure,
    • Wnt signaling