4YJE

Crystal structure of APC-ARM in complexed with Amer1-A1

Summary for 4YJE

• Entry DOI: 10.2210/pdb4yje/pdb
• Related: 4YJL 4YK6
• Descriptor: Adenomatous polyposis coli protein, APC membrane recruitment protein 1 (3 entities in total)
• Functional Keywords: armadillo-ligand complex, cell adhesion-protein binding complex, cell adhesion/protein binding
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell junction, adherens junction : P25054; Cytoplasm: Q5JTC6
• Total number of polymer chains: 2
• Total formula weight: 40387.49

Authors

Zhang, Z.,Xiao, Y.,Wu, G. (deposition date: 2015-03-03, release date: 2016-03-09, Last modification date: 2023-11-08)

Primary citation

Zhang, Z.,Akyildiz, S.,Xiao, Y.,Gai, Z.,An, Y.,Behrens, J.,Wu, G.
Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners
Cell Discov, 1:15016-15016, 2015

PubMed Abstract: The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC-Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM. In this study, crystal structures of APC-ARM in complexes with Amer1-A1, -A2, and -A4, which is newly identified in this work, were determined. Combined with our GST pull-down, yeast two-hybrid, and isothermal titration calorimetry (ITC) assay results using mutants of APC and Amer1 interface residues, our structures demonstrate that Amer1-A1, -A2, and -A4, as well as other APC-binding proteins such as Asef and Sam68, all employ a common recognition pattern to associate with APC-ARM. In contrast, Amer1-A3 binds to the C-terminal side of APC-ARM through a bipartite interaction mode. Composite mutations on either APC or Amer1 disrupting all four interfaces abrogated their association in cultured cells and impaired the membrane recruitment of APC by Amer1. Our study thus comprehensively elucidated the recognition mechanism between APC and Amer1, and revealed a consensus recognition sequence employed by various APC-ARM binding partners.

PubMed: 27462415
DOI: 10.1038/celldisc.2015.16

Experimental method

X-RAY DIFFRACTION (1.9 Å)