Continuous evolution of compact protein degradation tags regulated by selective molecular glues. (https://pubmed.ncbi.nlm.nih.gov/38484051/)

These scientists were trying to find a way to control the levels of specific proteins in cells. They discovered that a small piece of protein called a degron could be used to target and degrade other proteins. However, the degrons they were using were too big and had some unwanted effects.

So, the scientists came up with a new method called MG-PACE to evolve a smaller degron that could target proteins more precisely. They created a 36-amino acid degron called SD40 that could bind to a protein called cereblon when combined with a special molecule called PT-179.

By editing the genes of cells to include the SD40 degron, they were able to use PT-179 to specifically degrade certain proteins. They also used advanced imaging techniques to study how SD40 and cereblon interacted at a molecular level.

Overall, the scientists developed a new system to continuously improve these protein-targeting tools and created a smaller degron that could overcome the limitations of previous methods.

Mercer JAM., DeCarlo SJ., Roy Burman SS., Sreekanth V., Nelson AT., Hunkeler M., Chen PJ., Donovan KA., Kokkonda P., Tiwari PK., Shoba VM., Deb A., Choudhary A., Fischer ES., Liu DR. Continuous evolution of compact protein degradation tags regulated by selective molecular glues. Science. 2024 Mar 15;383(6688):eadk4422. doi: 10.1126/science.adk4422. Epub 2024 Mar 15.