Catching the action on the cell

Cell Biology For many proteins, specific proteolysis events are key to their function. This extends to the cell surface, where proteolysis of cell surface proteins can regulate communication between cells. There are several methods to isolate N-terminal peptides derived from proteolytic cleavage, but existing methods do not efficiently detect cleavage of cell surface proteins. Weeks et al. started with an enzyme called subtiligase, a tool developed to modify N termini, and fused it to a transmembrane domain to target it to the cell surface (subtiligase-TM). The subtiligase biotinylates the N termini, which can then be isolated and sequenced by mass spectrometry. This method can be used for identifying therapeutic targets and biomarkers. Proc. Natl. Acad. Sci. U.S.A. 118 , e2018809118 (2021).