Structural basis of the Axin-adenomatous polyposis coli interaction

Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the abse nce of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-on cogene beta-catenin through the formation of a large complex containing the se three proteins, glycogen synthase kinase 3 beta (GSK3 beta) 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 re sult in human cancers. A protease-resistant domain of Axin that contains th e APC-binding site is a member of the regulators of G-protein signaling (RG S) 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 fro m the G-protein interface of classical RGS proteins. The molecular interact ions observed in the Axin-APC complex provide a rationale for the evolution ary conservation seen in both proteins.