Scientists have found a way to rapidly move proteins to the ‘trash bin’ for research purposes. The new technique, called Trim-Away can remove protein from any cell type and also distinguish between different variants of a protein, opening the door for the technique to be used as disease treatment someday. The technique is described in a study released yesterday in the journal Cell.
Current methodologies for removing a protein to study its function in a cell rely on genome editing through CRISPR/Cas or RNA interference. While these methods are effective at shutting down a protein, they only affect protein amounts indirectly, are not applicable to every type of cell and protein and can be time consuming.
The new technique relies on a protein called MRC LMB: Trim21, which recognizes antibodies that enter the cell attached to viruses. It binds to the antibodies and tags the antibody-virus complex as 'garbage', then moves it to the proteasome for removal. Using this concept, the researchers introduced antibodies directed against a specific cellular protein into an egg cell. Trim21 recognized the antibody and delivered the antibody-bound protein to the proteasome. Within minutes, the protein was completely removed from the cell.
"Basically, Nature's toolbox provided us with all the components we needed. The trick was to choose the right ones and to combine them into a system that works for our purpose," said Melina Schuh, Director at the MPI for Biophysical Chemistry.
To get around the fact that many cell types only have limited amounts of Trim21, they delivered additional Trim21 protein into the cell along with the antibody and used a small electric shock to get the cell to take up the proteins.
The authors claim this will allow for removal of proteins in situations where this was previously difficult, such as in macrophages. Macrophages are good at recognizing and removing foreign DNA and RNA, central components of other protein-deleting techniques. Additionally, because of the high specificity antibodies achieve, it is possible to distinguish between two different variants of the same protein using this technique.