EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.

ABSTRACT: Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD). However, recent studies have demonstrated that EDEM1 binds to some misfolded proteins in a glycan-independent manner, suggesting a more complex binding landscape for EDEM1. In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α₁-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys²⁵⁶), required for binding under stringent detergent conditions. In addition to the thiol-dependent interaction, the presence

SUBMITTER: Lamriben L 

PROVIDER: S-EPMC6130956 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature