The 15-Amino Acid Repeat Region of Adenomatous Polyposis Coli Is Intrinsically Disordered and Retains Conformational Flexibility upon Binding ß-Catenin.
Biochemistry
; 59(41): 4039-4050, 2020 10 20.
Article
en En
| MEDLINE
| ID: mdl-32941008
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 ß-catenin destruction. This destruction is mediated by ß-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 â¼200-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 ß-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 ß-catenin and that APC does not have a single, observable "highest-affinity" binding site for ß-catenin. This flexibility potentially allows ß-catenin to be more readily captured by APC and then remain accessible to other elements of the destruction complex for subsequent processing.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína de la Poliposis Adenomatosa del Colon
/
Beta Catenina
Límite:
Humans
Idioma:
En
Revista:
Biochemistry
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos