Protein Folding and ER Quality Control Quiz

Protein Folding and Quality Control in the Endoplasmic Reticulum

• Oligosaccharyl transferases catalyze protein glycosylation in the endoplasmic reticulum (ER)
• Different polypeptides have unique folding pathways determined by their sequences
• Chaperones like BiP and folding proteins like Calnexin and Calreticulin assist in protein folding in the ER
• Disulfide bonds (DBs) play a key role in stabilizing the structure of secretory and membrane proteins
• Properly folded proteins are transported from the ER to the Golgi, while misfolded proteins are degraded in the cytosol
• Proteins can be translocated into the ER cotranslationally or posttranslationally
• Plasma membrane glycoproteins and soluble proteins destined for the ER have specific translocation processes
• ER resident proteins containing KDEL sequences are selectively transported back to the ER from the Golgi
• ER stress, caused by various conditions, leads to proteotoxicity and activates the unfolded protein response (UPR)
• The UPR includes transcriptional induction of chaperones, translational attenuation, ER-associated degradation (ERAD), and apoptosis in severe cases
• ER stress is associated with various pathophysiological conditions like ischemia, diabetes, and neurodegenerative diseases
• The UPR is a self-protective mechanism against ER stress, aiming to restore ER function and prevent cell death

Protein Targeting and Signal Hypothesis

• Protein targeting is essential for correct activity of newly synthesized proteins in both prokaryotes and eukaryotes
• Sorting or translocation of proteins can occur through co-translational or post-translational translocation processes
• Co-translational targeting occurs for proteins destined for the endoplasmic reticulum (ER), Golgi, lysosomes, plasma membrane, and secreted proteins
• Post-translational targeting occurs for proteins destined for the nucleus, mitochondria, and peroxisomes
• Proteins related to the GER include those that are secreted from the cell, lysosomal enzymes, and plasma membrane glycoproteins
• Targeting signals, such as signal sequences or signal peptides, enable the cellular transport machinery to correctly position proteins inside or outside the cell
• Proteins with signal sequences are synthesized on ribosomes attached to the ER membrane
• Signal peptides are recognized by signal recognition particles (SRP) in the cytosol, which then take the ribosome to the ER
• The interaction between the signal sequence and the ER membrane is believed to open a channel for polypeptide transport into the ER lumen
• Newly synthesized polypeptides in the ER undergo specific proteolytic cleavages, addition and processing of carbohydrates, proper folding, and assembly into multimeric proteins
• Specific proteolytic cleavages are carried out by signal peptidase
• Many secreted and membrane proteins contain covalently attached carbohydrates, which are added and processed in the ER and Golgi Complex