Time to look up from the plow biochemists. Everyone knows that ubiquitin is added to proteins to destroy them. The carboxy terminal amino acid of ubiquitin (glycine) forms an amide with the epsilon amino acid of a lysine called an isopeptide bond, and off the protein goes to the proteasome for destruction. This is simplistic and ubiquitination has many other other roles in the cell, but there isn’t time for it here.
I couldn’t resist putting in two interesting facts about ubiquitin.
#1. Like sharks, evolution hasn’t changed ubiquitin much — only 3/71 amino acids differ between yeast and us.
#2 Ubiquitin is so stable that boiling water doesn’t denature it < Science vol. 365 pp. 502 – 505 ’19 >.
We have over 600 E3 enzymes (ubiquitin ligases), 40 E2 enzymes, and 8 E1 enzymes, and all 3 types are required to add ubiquitin to proteins.
Once a bacterium gets inside a cell, one of the ways the innate immune system attacks it is by ubiquitinating its proteins. Nothing out of the ordinary there.
Salmonella (the organism responsible for most cases of food poisoning) is one such. Our cells ubiquitinate the hell out of it. However Nature vol. 594 pp. 28 – 29, 111 – 116 ’21 shows that, not just Salmonella proteins are the only sites of ubiquitination. We also ubiquitinate endotoxin (lipopolysaccharide) which is a combination of sugars and lipids, with nary an amino acid in sight. Endotoxin is a component of the outer membrane of every Gram negative bacterium, so the effect is likely not confined to Salmonella.
Even more spectacular is the enzyme adding ubiquitin. It is called RNF213 (aka Mysterin), which looks like nothing the classic E3 enzymes we know and love. For one thing in addition to E3 activity, it has a motor domain, a zinc binding domain and other domains of unknown function. It’s a real monster with 5,184 amino acids and a molecular mass of 584 kiloDaltons.
There is a lot of interesting molecular biology to RNF213 — mutations cause Moya moya disease.
But the papers are particularly interesting because they show a lot of work of a new type needs to be done.
What else does Mysterin ubiquitinate? Are there other enzymes in the cell adding ubiquitin, and if so, what do they ubiquitinate?
Definitely time to expand the well plowed field of ubiquitin.
Chemiotics II 