Redox Control of N‐linked Protein Glycosylation

Abstract

The Endoplasmic Reticulum (ER) is the cellular compartment where proteins are folded and glycosylated. This compartment is characterized by very intense and diverged redox processes that are catalyzed by numerous thiol oxidoreductases. Asparagine‐linked glycosylation is an essential redox‐regulated process of posttranslational protein modification within the ER, catalyzed by the multiprotein complex known as oligosaccharyltransferase (OST). The functions of most of the OST subunits are poorly understood. OST3/6‐like proteins are thioredoxin fold ER membrane‐linked thiol oxidoreductases involved in redox control of N‐linked protein glycosylation as components of OST complex. The exact biological function of these subunits is not well defined. The purpose of this research is to demonstrate the biological roles of OST3/6 – like proteins, clarify their contribution in metal metabolism and determine the impact of OST3/6 proteins deficiency in ER stress development. OST3/6 mutants show affected growth rate, cell wall integrity and presence of ER stress. We demonstrated that the OST3/6 double mutant is not viable, but OST3/6 mammalian homologs, IAP and N33, and reductases (TRXs) or isomerases (PDIs) can complement OST 3/6 mutation. Thus, OST3/6 –like proteins can serve as strong reductases or weak isomerases. This work was supported by NSF grant DBI‐ 1156692 and the Redox Biology Center REU program.