Overview
This lecture explains how proteins are modified after translation, increasing the diversity and regulation of protein function in the body beyond what is determined by genes alone.
Central Dogma & Protein Diversity
- The central dogma describes DNA being transcribed into RNA, then translated into protein.
- Post-translational modifications (PTMs) are changes made to proteins after translation.
- PTMs add variation, creating a "proteome," which is all proteins an organism can express.
- The proteome is larger than the genome due to alternative splicing and PTMs.
- PTMs can affect how proteins fold, their location, stability, and activity.
Types of Post-Translational Modifications
- Methylation: Adds a hydrophobic methyl group; affects folding and can play a role in gene regulation (epigenetics).
- Acetylation: Adds an acetyl group, often to the N-terminus; ~90% of human proteins can be acetylated, influencing their function.
- Glycosylation: Adds sugar groups (mono- or polysaccharides); affects folding, distribution, signaling, conformation, stability, and activity.
- Lipidation: Adds lipid group(s) to target proteins to membrane-rich areas like organelles or cell membranes.
- Ubiquitination: Attaches ubiquitin to proteins, often marking them for degradation.
- Phosphorylation: Adds phosphate groups via kinases/phosphatases; important in cell cycle, signaling, growth, and apoptosis.
- Proteolytic Cleavage: Proteins are cut by proteases (e.g., pepsinogen to pepsin) to activate or specialize their function.
Key Terms & Definitions
- Post-Translational Modification (PTM) — Chemical changes to proteins after translation that alter their function or location.
- Proteome — The entire set of proteins that an organism can express.
- Alternative Splicing — Process where different combinations of exons are joined to make various mRNA transcripts from a single gene.
- Methylation — Addition of a methyl group to a protein.
- Acetylation — Addition of an acetyl group to a protein.
- Glycosylation — Addition of sugar molecules to a protein.
- Lipidation — Attachment of lipid groups to a protein.
- Ubiquitination — Tagging a protein for degradation with ubiquitin.
- Phosphorylation — Addition of a phosphate group, often regulating activity.
- Proteolytic Cleavage — Cutting of proteins by enzymes (proteases).
Action Items / Next Steps
- Review main PTMs and their effects on protein function.
- Understand how PTMs increase protein diversity beyond what is coded by genes.
- No memorization of every possible modification required—focus on main concepts.