Multivalent Interaction of Beta-Catenin With its Intrinsically Disordered Binding Partner Adenomatous Polyposis Coli.
Rowling, Pamela JE
Murton, Ben L
Itzhaki, Laura S
Front Mol Biosci
Frontiers Media SA
MetadataShow full item record
Rowling, P. J., Murton, B. L., Du, Z., & Itzhaki, L. S. (2022). Multivalent Interaction of Beta-Catenin With its Intrinsically Disordered Binding Partner Adenomatous Polyposis Coli.. Front Mol Biosci, 9 https://doi.org/10.3389/fmolb.2022.896493
The Wnt signalling pathway plays key roles in cell proliferation, differentiation and fate decisions in embryonic development and maintenance of adult tissues, and the twelve Armadillo (ARM) repeat-containing protein β-catenin acts as the signal transducer in this pathway. Here we investigate the interaction between β-catenin's ARM repeat domain and the intrinsically disordered protein adenomatous polyposis coli (APC). APC is a giant multivalent scaffold that brings together the different components of the so-called "β-catenin destruction complex", which drives β-catenin degradation via the ubiquitin-proteasome pathway. Mutations and truncations in APC, resulting in loss of APC function and hence elevated β-catenin levels and upregulation of Wnt signalling, are associated with numerous cancers including colorectal carcinomas. APC has a long intrinsically disordered region (IDR) that contains a series of 15-residue and 20-residue binding regions for β-catenin. Here we explore the multivalent nature of the interaction of β-catenin with the highest affinity APC repeat, both at equilibrium and under kinetic conditions. We use a combination of single-site substitutions, deletions and insertions to dissect the mechanism of molecular recognition and the roles of the three β-catenin-binding subdomains of APC.
Molecular Biosciences, beta-catenin (β-catenin), adenomatous polyposis coli (APC), intrinsically disordered protein, protein-protein interaction (PPI), multivalency, fuzzy binding, armadillo repeat
External DOI: https://doi.org/10.3389/fmolb.2022.896493
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338457