The Origin of Specificity in Regulated Protein Degradation
One of the characteristic features of life — specificity — emerges in metabolism, information transfer from DNA to protein, embryology, immunology and virtually every other process. Its explanation on the molecular level is thermodynamic stability and structural complementarity. Yet one disturbing issue persists: the protein and nucleic acid sequences coding for that specificity are generally too small to distinguish actual partners from competitors. Similarly, protein degradation conveys specificity through very short sequences. The process is so kinetically complex that bulk kinetic experiments and a few molecular structures are insufficient to explain how specificity is achieved. Using single molecule kinetic measurements, we have deconvolved much of that specificity.