14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains.

ABSTRACT: Neural precursor cell expressed developmentally down-regulated 4 ligase (Nedd4-2) is an E3 ubiquitin ligase that targets proteins for ubiquitination and endocytosis, thereby regulating numerous ion channels, membrane receptors and tumor suppressors. Nedd4-2 activity is regulated by autoinhibition, calcium binding, oxidative stress, substrate binding, phosphorylation and 14-3-3 protein binding. However, the structural basis of 14-3-3-mediated Nedd4-2 regulation remains poorly understood. Here, we combined several techniques of integrative structural biology to characterize Nedd4-2 and its complex with 14-3-3. We demonstrate that phosphorylated Ser³⁴² and Ser⁴⁴⁸ are the key residues that facilitate 14-3-3 protein binding to Nedd4-2 and that 14-3-3 protein binding induce

SUBMITTER: Pohl P 

PROVIDER: S-EPMC8298602 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature