Destabilization domain(DD) is a strategy to combine a peptide sequence to a protein, which makes it unstable and vulnerable to proteasome for degradation. Upon binding of ligand with DD, the whole peptide sequence become stable and retain the function of target protein.

1. Nature Methods volume 4, pages1007–1009 (2007)

2. Investigative Ophthalmology & Visual Science October volume 59, 4909-4920. (2018)

3. Int J Parasitol. 2014 Sep; 44(10): 729–735.

None of these article explained clear mechanism of DD.

For what I want to know is, why DD fused protein is unstable? through which mechanism (incorrect folding structure, lysine exposed for ubiquitin recognition, etc.)?

Please enlighten me.