dc.contributor.author | Rudeen, Aaron J. | |
dc.contributor.author | Douglas, Justin T. | |
dc.contributor.author | Xing, Minli | |
dc.contributor.author | McDonald, W. Hayes | |
dc.contributor.author | Lamb, Audrey L. | |
dc.contributor.author | Neufeld, Kristi L. | |
dc.date.accessioned | 2022-02-09T17:01:01Z | |
dc.date.available | 2022-02-09T17:01:01Z | |
dc.date.issued | 2020-10-20 | |
dc.identifier.citation | Rudeen, A. J., Douglas, J. T., Xing, M., McDonald, W. H., Lamb, A. L., & Neufeld, K. L. (2020). The 15-Amino Acid Repeat Region of Adenomatous Polyposis Coli Is Intrinsically Disordered and Retains Conformational Flexibility upon Binding β-Catenin. Biochemistry, 59(41), 4039–4050. https://doi.org/10.1021/acs.biochem.0c00479 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32520 | |
dc.description | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biochem.0c00479. | en_US |
dc.description.abstract | The tumor suppressor Adenomatous polyposis coli (APC) is a large, multidomain protein with many identified cellular functions. The best characterized role of APC is to scaffold a protein complex that negatively regulates Wnt signaling via β-catenin destruction. This destruction is mediated by β-catenin binding to centrally located 15- and 20-amino acid repeat regions of APC. More than 80% of cancers of the colon and rectum present with an APC mutation. Most carcinomas with mutant APC express a truncated APC protein that retains the ∼200-amino acid long′ 15-amino acid repeat region′. This study demonstrates that the 15-amino acid repeat region of APC is intrinsically disordered. We investigated the backbone dynamics in the presence of β-catenin and predicted residues that may contribute to transient secondary features. This study reveals that the 15-amino acid region of APC retains flexibility upon binding β-catenin and that APC does not have a single, observable “highest-affinity” binding site for β-catenin. This flexibility potentially allows β-catenin to be more readily captured by APC and then remain accessible to other elements of the destruction complex for subsequent processing. | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | Copyright © 2020 American Chemical Society. | en_US |
dc.subject | APC | en_US |
dc.subject | Intrinsically Disordered Protein | en_US |
dc.subject | β-catenin | en_US |
dc.subject | Cancer Biology | en_US |
dc.subject | Stoichiometry | en_US |
dc.subject | NMR | en_US |
dc.subject | Structure-Function | en_US |
dc.title | The 15-aa repeat region of Adenomatous polyposis coli is intrinsically disordered and retains conformational flexibility upon binding β-catenin | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Rudeen, Aaron J. | |
kusw.kuauthor | Douglas, Justin T. | |
kusw.kuauthor | Xing, Minli | |
kusw.kuauthor | Lamb, Audrey L. | |
kusw.kuauthor | Neufeld, Kristi L. | |
kusw.kudepartment | Molecular Biosciences | en_US |
kusw.kudepartment | Nuclear Magnetic Resonance Core Laboratory | en_US |
dc.identifier.doi | 10.1021/acs.biochem.0c00479 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC8771494 | en_US |
dc.rights.accessrights | openAccess | en_US |