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First published online October 30, 2006
doi: 10.1242/10.1242/jcs.03225

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N-glycan processing in ER quality control

¹ Biocenter Oulu and Department of Biochemistry, University of Oulu, FIN-90014 Oulu, Finland
² Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland

View larger version (16K): [in a new window]   Fig. 1. Core glycans added on protein nascent chains. (A) The complete oligosaccharide is composed of two N-acetylglucosamine residues (black squares), nine mannose residues (green circles), and three glucose residues (red triangles). Linkages are shown and the three N-glycan branches are labeled A,B and C. (B) The absence of Dol-P-Man in the B3F7 cell line results in the transfer of a precursor structure missing four of the nine mannose residues but retaining the 1,2-mannose A.

View larger version (78K): [in a new window]   Fig. 2. Glycan processing determines the fate of the associated polypeptide chain. After addition of the pre-assembled oligosaccharide the two outermost glucoses are removed (step 1) and the nascent polypeptide associates with calnexin/calreticulin (Cnx) and the oxidoreductase ERp57. Most glycopolypeptides are probably released as native proteins (step 2) and exit the ER (step 3). Folding-defective polypeptides enter cycles of dissociation/re-association (steps 2a, 4 and 5) with Cnx. Folding attempts are eventually interrupted upon extensive substrate demannosylation and terminally misfolded polypeptides are retrotranslocated into the cytosol and degraded (step 6).

View larger version (27K): [in a new window]   Fig. 3. Similarities between EDEMs and ER -mannosidase I. (A) EDEM1, EDEM2, EDEM 3 and ER -mannosidase I (MA1B1) share sequence similarity within a region containing the ()7 barrel catalytic domain of class I mannosidases (family 47GH), shown in yellow. The N- and C-regions of the EDEM proteins beyond this domain share no similarity with MA1B1 or significant sequence similarity with each other. MA1B1 contains a transmembrane region, shown in red, which the EDEM proteins lack. The N-terminus of MA1B1 is cytosolic. (B) Sequence conservation between EDEM proteins and MA1B1. Residues highlighted in yellow on the structure of MA1B1 [based on Vallee et al. (Vallee et al., 2000)] are conserved; note the clustering of conserved residues around the active site. The calcium atom seen in the active site is light blue. (C) Back view of the protein in B. (D) Sequence conservation around the active site of the EDEM proteins and MA1B1. Residues within 6Å of kifunensine (pink) in the structure of MA1B1 with kifunensine bound [based on Vallee et al. (Vallee et al., 2000)] are shown. Residues highlighted in yellow are conserved; two residues whose side chains do not point towards kifunensine are not conserved (grey). The calcium ion is in light blue.

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