1deb

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spinqualitylabelsall models 1deb, resolution 2.4Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF THE N-TERMINAL COILED COIL DOMAIN FROM APC

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Adenoma, periampullary OMIM:[175100], Adenomatous polyposis coli OMIM:[175100], Adenomatous polyposis coli, attenuated OMIM:[175100], Colorectal cancer OMIM:[175100], Desmoid disease, hereditary OMIM:[175100], Gardner syndrome OMIM:[175100], Gastric cancer OMIM:[175100], Turcot syndrome OMIM:[175100]

About this Structure

1DEB is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of the amino-terminal coiled-coil domain of the APC tumor suppressor., Day CL, Alber T, J Mol Biol. 2000 Aug 4;301(1):147-56. PMID:10926498

Page seeded by OCA on Mon Nov 12 16:31:27 2007