Question

Cell Biology Short Answer Question: List the post-translational modifications that occur in the ER. Why are bacteria often a poor choice for the production of proteins for therapeutic purposes?

Answer 1

Post-translational modification that occur in the ER are:

(a) Glycosylation: covalent addition and processing of carbohydrates. N-linked or O-linked oligosaccharides are carbohydrates that are added to proteins to form glycoproteins, which are commonly used for cell-surface signaling.

(b) Formation of disulfide bonds: Disulfide bonds help stabilize the tertiary and quaternary structure of proteins, and these bonds are formed in the ER by the oxidation reaction of sulfhydryl (thiol) groups between two cysteine residues.

(c) Proper folding of polypeptide chains and assembly of multi-subunit proteins: Sequential actions of ER lumen proteins, protein folding enzymes, enables efficient folding of polypeptide chains into mature, folded proteins.

(d) Specific proteolytic cleavage: Unassembled or misfolded proteins are transported to the cytosol for degradation. ER membrane proteins recognizes the incorrectly folded protein and target it for transport into the cytosol via the process of dislocation.

Bacteria are often a poor choice for production of therapeutic proteins because prokaryotic cells do not have an ER. Although the bacteria may be able to produce the unfolded polypeptide chain as precursor for a therapeutic protein, the bacteria would have no way to efficiently and quickly make sure the protein was correctly folded or bound to carbohydrates or to other protein subunits.

It is unlikely that very much of the mature folded protein could be produced efficiently by the bacteria. Eukaryotic cells with an ER are much more effective at ensuring correct and efficient protein folding and other post-translational modifications.