post-translational modification
Summary
A post-translational modification is a chemical change made to a protein after the ribosome has made it, such as phosphorylation, glycosylation, or cleavage. It can alter activity, location, or stability without changing the gene. Phosphorylation is a frequently tested, reversible example.
Detail
Meaning: After translation, enzymes can chemically alter a polypeptide. Common examples are phosphorylation of Ser, Thr, or Tyr by kinases (reversed by phosphatases), glycosylation in the ER and Golgi, proteolytic cleavage (zymogen activation, signal peptide removal), disulfide bond formation between cysteines, lipid attachment, acetylation or methylation of lysines, and ubiquitination, which often marks a protein for proteasome degradation. The gene's encoded sequence is unchanged, but the protein's activity, location, stability, or binding partners can change.
On the MCAT: A passage shows a protein switched by a kinase; predict that the added negative phosphate changes conformation and activity. You may be asked which modification is reversible (phosphorylation) or irreversible (cleavage), where glycosylation occurs (ER and Golgi, for secreted and membrane proteins), or which residues can carry a phosphate (those with hydroxyl groups). A protein that runs heavier on a gel than its sequence predicts hints at a modification.
Common confusion: Students treat it as a change to the gene or mRNA, or as a form of translational control. It acts on the protein itself, so the DNA and mRNA are unchanged. Also, modifications differ in reversibility: phosphorylation is readily reversed, while cleaving a peptide bond is not.
Sources
- Lehninger Principles of Biochemistry
- Biochemistry (Berg, Tymoczko, Gatto, Stryer)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.