Nanoparticles and photochemistry for Native-like transmembrane protein footprinting

Mass spectrometry based footprinting can probe higher order structure of proteins. We bond photocatalytic nanoparticles to a lipid bilayer that, upon laser irradiation, produce high local concentrations of radicals that penetrate the lipid layer made permeable by a simultaneous laser-initiated PB reaction. This approach achieves high footprinting coverage for membrane proteins in liposomes, helps locate both ligand-binding residues in a transporter and ligand-induced conformational changes, and reveals structural aspects of the flexible unbound state. Overall, this approach proves highly effective in intramembrane footprinting and forges a connection between materials science and biology.