Degron
Encyclopedia
A degron is a specific sequence of amino acids in a protein that directs the starting place of degradation. A degron sequence can occur at either the N or C-terminal region, these are called N-Degrons or C-degrons respectively.

A temperature sensitive degron takes advantage of the N-end rule
N-end rule
The N-end rule is a rule related to ubiquitination, discovered by Alexander Varshavsky in 1986. The rule, which states that the nature of the N-terminal amino acids of a protein is an important factor that governs its half-life , is applicable to both eukaryotic and prokaryotic organisms, but with...

 pathway, in which a destabilizing N-terminal residue dramatically decreases the in vivo
Vivo
-Computer and technology:* Video In Video Out* Vivo Software, streaming format, acquired in 1998 by RealNetworks* VivoActive, Vivo Software's video format* Vivo S.A., a major Brazilian mobile phone company...

 half-life of a protein. The degron is a fusion protein of ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

, arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...

, and DHFR. DHFR is dihydrofolate reductase, a mouse-derived enzyme that functions in the synthesis of thymine. It is also heat-labile - at a higher temperature of 37°, becomes slightly unfolded and exposes an internal lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

, the site of poly-ubiquitination. Proteolysis is highly processive, and the protein is degraded by the proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria.  In eukaryotes, they are located in the nucleus and the cytoplasm.  The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...

. The degron can be fused to a gene to produce the corresponding temperature-sensitive protein. It is portable, and can be transferred on a plasmid.
A ligand controllable degron takes advantage of a mutant form of FKBP12 protein that can be controlled using a synthetic ligand. Small molecule Shield1 binds specifically to the degron making it inactive. An inactive degron no longer promotes protein degradation. The degron is reactivated when the small molecule is removed by washing the cells and active protein degradation occurs through proteasome mediated proteolysis.

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