Lecture Notes: Protein Modification and Post-Translational Modifications

Introduction

• Topic: Protein modifications, specifically post-translational modifications (PTMs).
• Audience: Concepts relevant to both prokaryotes and eukaryotes.
• Purpose: To understand PTMs via examples.

Basics of Protein Folding and Modifications

• Post-translation: After translation, proteins undergo folding (primary, secondary, tertiary, quaternary structures).
• Protein Folding: Proteins may require additional modifications to become functional.
• PTMs: Chemical changes to proteins post-translation, covalent modifications driven by enzymatic reactions.

Importance of PTMs

• Functions: Affect protein stability, activity, localization, and interactions with other biomolecules.
• Protein Diversity: PTMs increase protein diversity in cells.

PTM Mechanisms

• Categories:
  1. Functional Group Addition: Methylation, Acetylation, etc.
  2. Protein Tagging: Ubiquitination, Sumoilation.
  3. Backbone Cleavage: Proteolysis, Protein splicing.
  4. Amino Acid Changes: Oxidation, Deamination.

Common PTMs and Examples

• Phosphorylation

  • Common in signaling pathways, cell cycle.
  • Enzyme: Kinase.
  • Example: Epidermal growth factor receptor and downstream pathway (RAF, MEK, ERK).
  • Substrate: ATP.

• Methylation & Acetylation

  • Transfer of methyl/acetyl groups, common in histones.
  • Function: Regulate DNA accessibility, chromatin state.
  • Substrates: SAM for methylation, Acetyl Coenzyme A for acetylation.

• Glycosylation

  • Addition of sugar molecules, involved in protein folding and stability.
  • Example: Glycoproteins in blood cells defining blood groups.

• Ubiquitination

  • Addition of ubiquitin for protein degradation.
  • Proteasome: Degrades tagged proteins.
  • Prokaryotic Analog: Pup proteins.

• Sumoilation

  • Addition of SUMO tags, involved in protein transport and stability.
  • Example: Centrosome movement during cell cycle.

• Proteolysis

  • Cleavage of peptide bonds.
  • Example: Insulin production, blood clot formation.
  • Enzymes: Proteases.

• Protein Splicing

  • Removal of amino acid sequences (analogous to RNA splicing).
  • Presence: Common in lower eukaryotes and bacteria, not in humans.

PTMs and Diseases

• Defects: Can result in diseases such as cancer, liver cirrhosis, and blood clotting problems.
• Examples:
  • Methylation/acetylation defects in proto-oncogenes.
  • Glycosylation issues affecting immunity.
  • Ubiquitination problems leading to uncontrolled cell proliferation.

Conclusion

• Summary: PTMs play a crucial role in protein function and cellular processes.
• Impact: Defects in PTMs are associated with various diseases, emphasizing their biological significance.

Note

These notes provide a comprehensive overview of protein modifications, focusing on the importance and examples of various post-translational modifications and their implications in health and disease.