Discovery of metal-binding proteins by thermal proteome profiling.

Metal-binding proteins (MBPs) play diverse and critical functions in all living systems and many human diseases are closely related to dysfunctional MBPs. Here we developed a chemoproteomic method named METAL-TPP for global discovery of MBPs in proteomes, which operates by extracting metals from MBPs with chelators and logging the resulting structural perturbation of MBPs with thermal proteome profiling. We applied METAL-TPP to the human proteomes and identified 2856 proteins with significant thermal shifts, including not only many known MBPs but also 75 proteins without previous annotation of metal-binding activity.