In vitro mannosidase activity of EDEM3 against asparagine-linked oligomannose-type glycans

Oligomannose-type glycans on glycoproteins play an important role in the endoplasmic reticulum (ER) protein quality control. Mannose trimming of the glycans triggers the ER-associated protein degradation pathway. In mammals, ER mannosyl-oligosaccharide 1,2-alpha-mannosidase 1 and three ER degradation-enhancing alpha-mannosidase-like proteins (EDEMs) are responsible for mannose trimming. However, the exact role of EDEMs as alpha-mannosidases in ERAD remains unclear. Here, we performed the biochemical characterization of EDEM3 using synthetic oligomannose-type glycan substrates. In vitro assays revealed that EDEM3 can convert an asparagine-linked M9 glycan to M8 and M7 glycans in contrast to glycinelinked M9 glycan, and the activity is enhanced in the presence of ERp46, a known partner protein of EDEM3. Our study provides novel insights into the enzymatic properties of EDEM3 and the use of artificial glycan substrates as tools to study ERAD mechanisms. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

It has been discovered that EDEM3 plays a significant role in the protein quality control in the endoplasmic reticulum (ER), by converting specific glycans into other types of glycans. Additionally, the activity of EDEM3 is enhanced through interaction with ERp46. This study provides new insights into the enzymatic properties of EDEM3 and the use of artificial glycan substrates to study ERAD mechanisms.