Glycoprotein Folding and Processing Reactions

Abstract

The N-glycan-dependent quality control of glycoprotein folding occurring in the endoplasmic reticulum prevents exit to Golgi of folding intermediates, irreparably misfolded glycoproteins, and incompletely assembled multimeric complexes. It also enhances folding efficiency by preventing aggregation and facilitating formation of proper disulfide bonds. The control mechanism essentially involves four components, two resident lectin-chaperones, calnexin and calreticulin, that recognize monoglucosylated polymannose protein-linked glycans, a lectin-associated oxidoreductase acting on monoglucosylated glycoproteins, a glucosyltransferase that creates monoglucosytlated epitopes in protein-linked glycans, and a glucosidase that removes the glucose units added by the glucosyltransferase. The glucosyltransferase is the only mechanism component sensing glycoprotein conformations as it creates monoglucosylated glycans exclusively in not properly folded species or in not completely assembled complexes. The glucosidase is a heterodimer composed of a catalytic subunit and an additional one that is responsible for the ER localization of the enzyme. The glucosyltransferase, the glucosidase, and calreticulin, but not calnexin, are soluble proteins.