N-glycosylation in the protease domain of trypsin-like serine proteases mediates calnexin-assisted protein folding

eLife

Shuo Li¹  Qingyu Wu²  Juejin Wang²  Shenghan Chen²  Xue-Long Sun²  Hao Wang² 

[1] Department of Chemistry, Cleveland State University, Cleveland, United States;Molecular Cardiology, Cleveland Clinic, Cleveland, United States;

关键词: calnexin;    corin;    N-glycosylation;    protein folding;    serine protease;   

DOI  :  10.7554/eLife.35672

来源: DOAJ

【 摘 要 】

Trypsin-like serine proteases are essential in physiological processes. Studies have shown that N-glycans are important for serine protease expression and secretion, but the underlying mechanisms are poorly understood. Here, we report a common mechanism of N-glycosylation in the protease domains of corin, enteropeptidase and prothrombin in calnexin-mediated glycoprotein folding and extracellular expression. This mechanism, which is independent of calreticulin and operates in a domain-autonomous manner, involves two steps: direct calnexin binding to target proteins and subsequent calnexin binding to monoglucosylated N-glycans. Elimination of N-glycosylation sites in the protease domains of corin, enteropeptidase and prothrombin inhibits corin and enteropeptidase cell surface expression and prothrombin secretion in transfected HEK293 cells. Similarly, knocking down calnexin expression in cultured cardiomyocytes and hepatocytes reduced corin cell surface expression and prothrombin secretion, respectively. Our results suggest that this may be a general mechanism in the trypsin-like serine proteases with N-glycosylation sites in their protease domains.

【 授权许可】

Unknown