The crystal structure of an inactive dimer of PDZ-binding kinase.
Biochem Biophys Res Commun
; 476(4): 586-593, 2016 08 05.
Article
en En
| MEDLINE
| ID: mdl-27262437
ABSTRACT
The overexpression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) has been associated with hematologic tumors, breast cancer and various other cancers. However, the three-dimensional structure of PBK has not been solved. In this study, we determined the crystal structure of human PBK, which has two phospho-mimicking mutations T9E and T198E. The structural data indicated that PBK may assemble into an inactive dimer in alkaline conditions. Analytical size-exclusion chromatography and analytical ultracentrifugation confirmed that PBK exists in a conformational transition between dimers and monomers at different pH conditions. Co-IP and kinase assays suggested that the active state of PBK is a monomer and does not form a dimer even under alkaline conditions. These results showed that the conformational transition of PBK is important for its kinase activity regulation. Collectively, our observations may provide a novel starting point for structure-based functional studies.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Quinasas de Proteína Quinasa Activadas por Mitógenos
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2016
Tipo del documento:
Article
País de afiliación:
China