Folding of glycoproteins entering the secretory pathway is strictly surveyed in the endoplasmic reticulum by a quality control system. Folding intermediates and proteins irreparably misfolded are marked via glucosylation by the UDPglucose:glycoprotein glucosyltransferase, an enzyme that acts as a folding sensor by exclusively labeling glycoproteins not displaying their native structures. Here we show that this sensing mechanism also applies to the oligomerization of protein complexes, as the glucosyltransferase appeared to be able to glucosylate folded complex subunits lacking the full complement of oligomer components.Newly synthesized proteins must complete folding before they move through the secretory pathway. A quality control mechanism retains misfolded and unassembled species in the endoplasmic reticulum (ER) 1 (1, 2). This system is composed of four main elements, the ER resident lectins calnexin and calreticulin and the enzymes glucosidase II and UDPglucose:glycoprotein glucosyltransferase (GT). About 80% of proteins entering the secretory pathway are N-glycosylated cotranslationally in the consensus sequence Asn-X-(Ser/Thr). The two outermost glucoses are removed from the transferred glycan (Glc 3 Man 9 GlcNAc 2 ) by the sequential action of glucosidase I and glucosidase II. The monoglucosylated species thus generated are then recognized by calnexin and/or calreticulin, which are lectins specific for Glc 1 Man 5-9 GlcNAc 2 glycans (3). The glycoprotein-lectin association not only retains in the ER the species that are not properly folded but also enhances folding efficiency by preventing the aggregation of intermediates and allowing the action of other folding-enhancing proteins such as ERp57, a protein disulfide isomerase associated with calnexin and calreticulin (4). The glycoprotein-lectin interaction is eventually terminated upon glucosidase II cleavage of the remaining glucose. At this stage, glycoproteins that are properly folded proceed to their final destination. Folding intermediates or irreparably misfolded glycoproteins, however, are reglucosylated by GT, an enzyme that recreates the monoglucosylated structure, and are thus retained by the lectins in the ER. GT operates as a folding sensor, because it only glucosylates glycoproteins not displaying their native structures (5). Protein determinants triggering GT-mediated glucosylation have been identified as patches of hydrophobic amino acids that are mainly solvent-exposed in molten globule-like conformations (6).It has been observed in vivo that only fully assembled oligomeric proteins leave the ER. The above mentioned glycoprotein folding quality control mechanism has been implicated in the retention of individual subunits or partially assembled oligomers, because those species have been isolated as being associated to calnexin/calreticulin from cells unable to form the complete oligomers (7,8). For instance, the lectin-glycoprotein association of T cell receptor or human class I major histocompatibility complex components has been observed...