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A sweet code for glycoprotein folding
Author(s) -
Caramelo Julio J.,
Parodi Armando J.
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.07.021
Subject(s) - calnexin , glycoprotein , glycan , endoplasmic reticulum , chemistry , biochemistry , golgi apparatus , calreticulin , glycosylation , endoplasmic reticulum associated protein degradation , protein folding , glucosyltransferase , microbiology and biotechnology , enzyme , biology , unfolded protein response
Glycoprotein synthesis is initiated in the endoplasmic reticulum (ER) lumen upon transfer of a glycan (Glc 3 Man 9 GlcNAc 2 ) from a lipid derivative to Asn residues ( N ‐glycosylation). N ‐Glycan‐dependent quality control of glycoprotein folding in the ER 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, resident lectin‐chaperones (calnexin and calreticulin) that recognize monoglucosylated polymannose protein‐linked glycans, lectin‐associated oxidoreductase acting on monoglucosylated glycoproteins (ERp57), a glucosyltransferase that creates monoglucosylated epitopes in protein‐linked glycans (UGGT) and a glucosidase (GII) that removes the glucose units added by UGGT. This last enzyme is the only mechanism component sensing glycoprotein conformations as it creates monoglucosylated glycans exclusively in not properly folded glycoproteins or in not completely assembled multimeric glycoprotein complexes. Glycoproteins that fail to properly fold are eventually driven to proteasomal degradation in the cytosol following the ER‐associated degradation pathway, in which the extent of N ‐glycan demannosylation by ER mannosidases play a relevant role in the identification of irreparably misfolded glycoproteins.