Key Concepts of Section 13.3

Protein Modifications, Folding, and Quality Control in the ER

• All N-linked oligosaccharides, which are bound to asparagine residues, contain a core of two N-acetylglucosamine and at least three mannose residues and usually have several branches. O-linked oligosaccharides, which are bound to serine or threonine residues, are generally short, often containing only one to four sugar residues.

• Formation of N-linked oligosaccharides begins with assembly of a conserved 14-residue high-mannose oligosaccharide precursor on dolichol, a lipid in the membrane of the rough ER (see Figure 13-17). After this preformed oligosaccharide is transferred to specific asparagine residues of nascent polypeptide chains in the ER lumen, three glucose residues and one mannose residue are removed (see Figure 13-18).

• Oligosaccharide side chains may assist in the proper folding of glycoproteins, help protect the mature proteins from proteolysis, participate in cell-cell adhesion, and function as antigens.

• Disulfide bonds are added to many soluble secretory proteins and to the exoplasmic domain of membrane proteins in the ER. Protein disulfide isomerase (PDI), present in the ER lumen, catalyzes both the formation and the rearrangement of disulfide bonds (see Figure 13-19).

• The chaperone BiP, the lectins calnexin and calreticulin, and peptidyl-prolyl isomerases work together to ensure proper folding of newly made secretory and membrane proteins in the ER. The subunits of multimeric proteins also assemble in the ER (see Figure 13-20).

• Only properly folded proteins and assembled subunits are transported from the rough ER to the Golgi complex in vesicles.

• The accumulation of abnormally folded proteins and unassembled subunits in the ER can induce increased expression of ER protein-folding catalysts via the unfolded-protein response (see Figure 13-21).

• Unassembled or misfolded proteins in the ER are often transported back to the cytosol, where they are degraded in the ubiquitin-proteasome pathway (see Figure 13-22).