Mannosidase activity of EDEM1 and EDEM2 depends on an unfolded state of their glycoprotein substrates.

ABSTRACT: Extensive mannose trimming of nascent glycoprotein N-glycans signals their targeting to endoplasmic reticulum-associated degradation (ERAD). ER mannosidase I (ERManI) and the EDEM protein family participate in this process. However, whether the EDEMs are truly mannosidases can be addressed only by measuring mannosidase activity in vitro. Here, we reveal EDEM1 and EDEM2 mannosidase activities in vitro. Whereas ERManI significantly trims free N-glycans, activity of the EDEMs is modest on free oligosaccharides and on glycoproteins. However, mannosidase activity of ERManI and the EDEMs is significantly higher on a denatured glycoprotein. The EDEMs associate with oxidoreductases, protein disulfide isomerase, and especially TXNDC11, enhancing mannosidase activity on glycoproteins but not on free

SUBMITTER: Shenkman M 

PROVIDER: S-EPMC6194124 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature