Term Tuesday: Proteasome

Today's term is Proteasome.  Never heard of it?  Cool.  Let's get started then.

 Like every good city, someone needs to take out the trash and the proteasome is the one to do it for a cell. The proteasome is the trash compactor and recycling center for proteins in a cell. The proteasome is a big, barrel shaped protein complex in a cell (we're talking eukaryotes here) that degrades and disassembles bad proteins.  By bad proteins, I mean proteins that were made or folded improperly, proteins that no longer are needed, and proteins that have been damaged, say by heat shock.

The proteasome is made up of several protein complexes that arrange themselves, I kid you not, like a kitchen trash can with a pop-up lid.  The details get my head spinning, so I'll probably not do justice to the amazing research behind discovering how it works.  But here it goes.  The main barrel of the proteasome trash can, called the 20S particle, is made of small proteins aggregating together to make rings. There's 7 rings in the barrel, and the outer two contain regulatory elements that can sense what proteins are entering to be degraded. The lid of the trash can, called the 19S regulatory cap, senses the proteins to be degraded and feeds them into the barrel.  It takes energy to destroy a protein and the energy comes in the form of using ATP, the main fuel in the cell.  The energy spent here is in the binding of the bad protein to the 19S and 20S particle.  There's yet another part of the trash can, the 11S particle, and it regulates degradation of short proteins or peptides.

Proteins are generally tagged for destruction by a small chemical modification called ubiquitin.  Attaching onto the amino acid Lysine, the ubiquitin is placed on there by yet another complex of proteins called ubiquitin ligase.  The ubiquitin ligase is the trash collector: it identifies the proteins in the cell that need to be recycled.  You guessed it, there's several proteins associated with ubiquitin ligase, and it's where the specificity comes into play. When a protein is tagged for destruction, it attaches to the 19S (or 11S if it's small) particle and is fed into the 20S particle.  It's here that it gets chewed into small peptide chains, which can be further degraded and recycled into new proteins.  Nice and tidy.

Proteasomal degradation of proteins plays a huge role in the normal control of cell division, homeostasis, and stress response.  However, sometimes the proteasome degradation process goes awry, and can lead to disease.  Too much proteasomal activity can lead, supposedly, to autoimmune disease.  Not enough can lead to things like Alzheimer's disease and cancer.

Remembering back to high school biology (quite a few years back, I won't tell you how many) I never learned about proteasomes. It's because they probably weren't identified yet as parts of the cell. They were only really discovered in the '80's.  And work that identified it was deemed worthy of the Nobel Prize in 2004.  Really, we all should celebrate those who know how to take out the trash.

P.S.  I'll get to actually putting in reference and attributions here soon.  I promise.