Dynamic networks connect the USP14 active site region with the proteasome interaction surface.

ABSTRACT: Ubiquitin-specific protease 14 (USP14) is a member of the USP family responsible for the catalytic removal of ubiquitin (Ub) from proteins directed to the proteasome, implicated in the pathogenesis of neurodegeneration and cancer. Crystallography and cryo-EM analysis have identified loop regions crucial for the deubiquitinase activity of USP14, specifically those involved in Ub and proteasome binding. However, the structural changes in USP14 upon ligand binding to these regions are minimal, indicating significant yet uncharacterized dynamic contributions to its function. In this study, through structural and dynamical NMR experiments and functional evaluation, we demonstrate that small mutations designed to impact Ub binding and catalytic activity without disturbing the USP structure displ

SUBMITTER: Salomonsson J 

PROVIDER: S-EPMC11912437 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature