The Power of the Proteasome

The proteasome is a crucial protein complex in cells that breaks down and recycles damaged or unneeded proteins. It’s a core part of the ubiquitin-proteasome system (UPS), which regulates protein quality control and maintains cellular homeostasis. Let’s break it down:

🌿 Structure

• The 26S proteasome is the most common form, made up of two main subcomplexes:
  • 20S core particle (CP): This barrel-shaped core contains the proteolytic (protein-degrading) sites. Proteins are broken down here into small peptides.
  • 19S regulatory particles (RP): These “caps” sit at one or both ends of the 20S core, recognizing proteins tagged for degradation and unfolding them so they can enter the core for breakdown.

⚡ Function

The proteasome’s main job is to degrade proteins that have been marked with a small protein called ubiquitin. This process is essential for:

• Removing damaged or misfolded proteins — preventing toxic build-up.
• Regulating protein levels — controlling the cell cycle, immune responses, and stress responses.
• Antigen processing — breaking down proteins into peptides that are presented to the immune system.

🏷️ How does the ubiquitin tag work?

1. Ubiquitination: A series of enzymes (E1, E2, and E3) attach a chain of ubiquitin molecules to a target protein.
2. Recognition: The 19S regulatory particle identifies the ubiquitinated protein.
3. Unfolding and translocation: The protein is unfolded and threaded into the 20S core.
4. Degradation: The 20S core chops the protein into small peptides (7–9 amino acids long).
5. Recycling: The peptides can be further broken down into amino acids for reuse.

🧬 Why is the proteasome important?

• Cancer: Proteasomes help regulate proteins that control cell growth. Overactive proteasomes can contribute to unchecked cell division, so proteasome inhibitors (like bortezomib) are used as cancer treatments.
• Neurodegenerative diseases: Impaired proteasome function is linked to diseases like Alzheimer’s and Parkinson’s, where misfolded proteins accumulate and damage neurons.
• Immunity: Specialized versions of the proteasome (called immunoproteasomes) help generate peptides for MHC class I molecules, which are essential for immune defense.