Read about Proteasomes and protein recycling
The Proteasome
Protein breakdown is just as essential to the cell as protein synthesis.
Four uses of the proteasome
- to supply amino acids for fresh protein synthesis,
- to remove excess enzymes,
- to remove cyclins for control of the cell cycle,
- to remove transcription factors that are no longer needed.
There are two major structures in cells which break down and recycle damaged or unneeded proteins.
They are lysosomes and proteasomes
Lysosomes
Lysosomes deal primarily with extracellular proteins, proteins that come from outside the cell.
e.g. proteins, that are taken into the cell by endocytosis.
Proteasomes
Proteasomes deal primarily with proteins that were synthesized within the cell.
Proteasomes also address proteins that are folded incorrectly because of translation errors, or they are encoded by faulty genes or they have been damaged by other molecules in the cytosol.
The structure of the proteasome includes a Core Particle and Regulatory Particles.
The core particle is made of 28 different proteins that are assembled in groups forming 4 rings stacked on each other (like 4 doughnuts) along a common center.
There are two identical regulatory particles, one at each end of the core particle. Each is made of 19 different proteins. Six of these are ATPases that use ATP to unfold the protein being recycled. Some of the subunits have sites that recognize the protein ubiquitin.
Ubiquitin is a small protein (76 amino acids) that is virtually identical in its amino acid sequence throughout all the kingdoms of life, including bacteria, yeast, and mammals. Ubiquitin is used by all these creatures to target proteins for destruction (hence its name, based on of the term "ubiquitous" - to be found everywhere).
The process of hydrolysis and recycling
Proteins destined for destruction are attached to a molecule of ubiquitin which binds to the terminal amino group of a lysine amino acid in the protein. Additional molecules of ubiquitin bind to the first forming a chain. This complex chain of ubiquitin molecules then binds to ubiquitin-recognizing site(s) on the regulatory particle which allows it to enter the proteasome.
The protein is unfolded by the ATPases using the energy of ATP. Then the protein is moved into the central cavity of the core particle. Several active sites on the inner surface of the two middle "doughnuts" break various specific peptide bonds of the chain. This produces a set of peptides averaging about 8 amino acids long. These leave the core particle and go into the cytoplasm (cytosol).
The small peptides may be further broken down into individual amino acids by peptidases in the cytosol.
Sometimes, in mammals, they may be presented to the immune system as a potential antigen.
The regulatory particle of the proteasome releases the ubiquitins for reuse.
The amino acids can be attached to tRNA molecules for the translation part of protein synthesis.
Antigen processing by Proteasomes
In mammals, activation of the immune system to recognise a specific antigen involves proteasomes.
In an immune response the proteasome is altered so that the peptides generated in this altered proteasome are picked up by a transporter proteins and taken into the endoplasmic reticulum after which they pass through the Golgi apparatus until they are finally inserted in the plasma membrane where it can be "recognized" by white blood cells, lymphocytes called T cells.