Protein domains/Degradation/Overview

Degradation tags are short peptide sequences that mark a protein for degradation by the cell's protein recycling machinery. In doing so, the degradation tag effectively decreases the protein half-life or the typical length of time that a protein, once translated, will exist in the cell. (Formally, the half-life is the interval time it takes for the level of the protein to decay to half its initial value.) In practice, adding a degradation tag will also tend to decrease the concentration of the protein in the cell.

Many of the degradation tags available via the Registry are "ssRA tags" which function in E. coli. In the natural system, ssRA tagging occurs when a ribosome gets stuck on a broken ("truncated") mRNA. Without a normal termination codon, the ribosome cannot detach from the defective mRNA. A special type of RNA known as ssRA ("small stable RNA A") or tmRNA ("transfer-messenger RNA") rescues the ribosome by adding an eleven codon degradation tag followed by a stop codon. This allows the ribosome to break free and continue functioning. The tagged, incomplete protein then gets degraded by the proteases ClpXP or ClpAP.

Although the originally identified ssRA/tmRNA tag had the sequence AANDENYALAA Keiler, additional designed degradation tags that vary in the final three amino acids (AAV, ASV, LVA, LAA) have since been found that result in different protein half-lives Andersen.