After translation, many proteins undergo posttranslational modifications (PTMs) to become functionally active. These modifications can alter a protein’s structure, localization, stability, and activity — critical for proper cellular function.
Trimming (Proteolytic Activation)
- Removal of N- or C-terminal peptide segments (propeptides) from inactive precursor molecules (zymogens), converting them into active enzymes.
| Process | Example | Purpose |
|---|---|---|
| Removal of propeptides from zymogens | Trypsinogen → Trypsin (in small intestine) | Activates digestive enzymes for protein breakdown |
| Cleavage of signal peptides | Preproinsulin → Proinsulin → Insulin | Enables correct folding and secretion |
Key Concept:
Without trimming, many enzymes remain inactive — a key regulatory mechanism in digestion and coagulation.
Covalent Alterations
Posttranslational covalent modifications regulate protein function, localization, and degradation.
| Modification | Description | Example / Clinical Relevance |
|---|---|---|
| Phosphorylation | Addition of phosphate group (via kinases) | Regulates enzyme activity; e.g., glycogen phosphorylase activation |
| Glycosylation | Addition of carbohydrate chains | Glycoproteins for cell recognition and stability |
| Hydroxylation | Addition of –OH to proline/lysine residues | Collagen synthesis (requires vitamin C) — deficiency → Scurvy |
| Methylation | Addition of –CH₃ to DNA or histones | Regulates gene expression (epigenetic control) |
| Acetylation | Addition of an acetyl group (often to histones) | Activates transcription by relaxing chromatin |
| Ubiquitination | Attachment of ubiquitin molecules | Targets proteins for proteasomal degradation |
Clinical Correlation
- Scurvy: Defective hydroxylation → unstable collagen → poor wound healing and bleeding gums.
- Cancer & Epigenetics: Dysregulated methylation or acetylation affects oncogene/tumor suppressor expression.
- Neurodegenerative disorders: Abnormal ubiquitination contributes to protein aggregation (e.g., Parkinson’s disease).
Learning Objective
By the end of this lesson, the learner should be able to:
Identify and describe major posttranslational modifications, their biochemical mechanisms, and related clinical implications.
