Dimer formation by an N-terminal coiled coil in the APC protein.
Mutations in the human APC gene are associated with an inherited predisposition to colon cancer. APC codes for polypeptides of approximately 2800 amino acids, with sequence homologies to coiled-coil proteins in the first 900 residues. To determine the oligomerization properties of the APC protein, we used genetic and biochemical approaches to examine the ability of APC fragments to self-associate. A subdomain comprising the first 55 amino acids of APC was found to form a stable, parallel, helical dimer, as expected for a coiled coil. The location of a key dimerization element at the N terminus of the protein supports models in which mutations in APC exert effects through dimerization of the mutant gene products.
Joslyn
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Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84132.
Richardson
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White
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Alber
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D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins
D025601:Adenomatous Polyposis Coli Protein; D004220:Disulfides; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011994:Recombinant Proteins