PELSA, developed by a team from the Dalian Institute of Chemical Physics and the Shanghai Institute of Materia Medica, is a novel proteomics technique highlighted for its capability to identify ligand-binding proteins and their binding sites in native environments, eliminating the need for ligand modification. This method offers greater sensitivity, particularly for low-affinity metabolite interactions, and has diverse applications in drug design and biological research. Traditional methods, which often require purified proteins, can suffer from inaccuracies due to changes in protein states that can occur during purification.
The peptide-centric local stability assay utilizes trypsin to generate small peptides from native proteins, with the resulting peptide abundance reflecting local stability and ligand-binding dynamics. PELSA’s enhanced sensitivity allows for the identification of over 40 target proteins for alpha-ketoglutarate in HeLa cell lysates, with many being well-known binding proteins, indicating reliability across various ligands including metabolites, drugs, and pollutants. Compared to existing techniques like LiP-MS and thermal proteome profiling, PELSA shows significantly improved performance in identifying binding targets and sites, making it a powerful tool for understanding protein-ligand interactions crucial for metabolic regulation and drug action.
