NSF C-GEM researchers and collaborators found a novel pathway for protein labeling using engineered aminoacyl-tRNA Synthetases (aaRS) and non-canonical amino acids (ncAAs). In the absence of their cognate tRNAs, engineered aaRSs can release reactive ncAA-AMP intermediates that covalently label nearby proteins. This system for proximity-dependent labeling has the potential to be especially useful in multiplexed proximity labeling, and demonstrates how important it is to control expression of engineered aaRSs and tRNAs in genetic code expansion.
This work involved contributions from the Chatterjee lab.