Oa AEP1-mediated PNA-protein conjugation enables erasable imaging of membrane proteins.

We report the use of a protein ligase to covalently ligate a protein to a peptide nucleic acid (PNA). The rapid ligation demands only an N-terminal GL dipeptide in the target protein and a C-terminal NGL tripeptide in the PNA. We demonstrate the versatility of this approach by attaching a PNA strand to three different proteins. Lastly, we show that erasable imaging of EGFR on HEK293 cell membranes is achieved with DNA origami nanostructures and toehold-mediated strand displacement.