STRUCTURE OF THE AXIN RGS-HOMOLOGOUS DOMAIN IN COMPLEX WITH A SAMP REPEAT FROM APC

File:1emu.jpg


PDB ID 1emu

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, resolution 1.90Å
Ligands:
Coordinates: save as pdb, mmCIF, xml



OverviewOverview

Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene beta-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3beta (GSK3beta) and several other proteins. Both Axin and APC are known to be critical for beta-catenin regulation, and truncations in APC that eliminate the Axin-binding site result in human cancers. A protease-resistant domain of Axin that contains the APC-binding site is a member of the regulators of G-protein signaling (RGS) superfamily. The crystal structures of this domain alone and in complex with an Axin-binding sequence from APC reveal that the Axin-APC interaction occurs at a conserved groove on a face of the protein that is distinct from the G-protein interface of classical RGS proteins. The molecular interactions observed in the Axin-APC complex provide a rationale for the evolutionary conservation seen in both proteins.

DiseaseDisease

Known diseases associated with this structure: Adenoma, periampullary OMIM:[611731], Adenomatous polyposis coli OMIM:[611731], Brain tumor-polyposis syndrome 2 OMIM:[611731], Caudal duplication anomaly OMIM:[603816], Colorectal cancer, somatic OMIM:[611731], Desmoid disease, hereditary OMIM:[611731], Gardner syndrome OMIM:[611731], Gastric cancer, somatic OMIM:[611731], Hepatoblastoma OMIM:[611731], Hepatocellular carcinoma, somatic OMIM:[603816]

About this StructureAbout this Structure

1EMU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis of the Axin-adenomatous polyposis coli interaction., Spink KE, Polakis P, Weis WI, EMBO J. 2000 May 15;19(10):2270-9. PMID:10811618

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