Storck, E. M. et al. Nat. Chem. https://doi.org/10.1038/s41557-019-0237-6 (2019).

Farnesyl transferase and geranylgeranyl transferase catalyze the attachment of a farnesyl or geranylgeranyl isoprenoid to a C-terminal cysteine motif in an irreversible post-translational process known as protein prenylation. Current approaches to study prenylation have had limited proteome coverage and poor selectivity. Storck et al. introduce a new approach to profile prenylation in cells by using chemical proteomics. They developed a pair of alkyne-containing probes named YnF and TnGG, which are metabolically incorporated into proteins; the alkyne tags allow such modified proteins to be affinity-purified via a click-chemistry reaction. Prenylated proteins can therefore be isolated and identified by liquid chromatography–mass spectrometry. In a human endothelial cell line, Storck et al. identified 80 prenylated proteins, many of which were previously unknown. They also applied the approach to study prenylation of Rab proteins in a mouse model of retinal disease (choroideremia).