After a protein is made, most proteins are further modified. Post-translational modifications (PTMs) expand the proteome’s functional diversity and regulate protein activity, location, and lifespan.
The Main Modifications
Modification
Chemistry
Purpose
Phosphorylation
Phosphate on Ser/Thr/Tyr
On/off switch for activity; fast, reversible
Glycosylation
Sugar chain on Asn (N-linked) or Ser/Thr (O-linked)
Activates zymogens, cleaves signal peptides, matures hormones
Signal Peptide and Secretion
Proteins destined for membranes, lysosomes, or secretion carry an N-terminal signal peptide. Signal recognition particle (SRP) recognizes the emerging peptide on the ribosome and docks it to the ER. The ribosome finishes translation while the nascent protein threads into the ER lumen. The signal peptide is then cleaved by signal peptidase.
Zymogen Activation (Review)
Chapter 2 introduced zymogens - inactive precursors activated by cleavage. Digestive proteases, clotting factors, and caspases are all activated this way. Irreversible cleavage is a committed “on” signal that cannot easily be undone.
What does polyubiquitination signal for a target protein?
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Degradation by the 26S proteasome. Short or single ubiquitin tags can alter protein location or activity, but long polyubiquitin chains (especially K48-linked) are recognized by the proteasome, which unfolds and cleaves the tagged protein into small peptides. Polyubiquitination is the cell's primary signal for regulated protein destruction.
How does a signal peptide direct a protein to the ER?
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The signal peptide is an N-terminal sequence of about 15-30 amino acids, often rich in hydrophobic residues. As it emerges from the ribosome, the signal recognition particle (SRP) binds it and pauses translation. The SRP-ribosome complex docks at the ER's SRP receptor; translation resumes as the peptide threads into the ER lumen. Signal peptidase then cleaves the signal peptide.
Why does histone acetylation activate transcription?
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Histones are positively charged (rich in lysine and arginine) and bind tightly to negatively charged DNA. Acetylating a lysine neutralizes its positive charge, weakening the histone-DNA interaction. The chromatin relaxes, making DNA more accessible to RNA polymerase and transcription factors. Histone deacetylases (HDACs) reverse this.
