Lighting Up and Identifying Metal-Binding Proteins in Cells

Metal ions, either essential or therapeutic, play critical roles in life processes or in the treatment of diseases. Proteins and enzymes are involved in metal homeostasis and the action of metallodrugs. Imaging and identifying these metal-binding proteins will facilitate the elucidation of metal-mediated life processes. The emerging research field of metallomics and metalloproteomics has significantly advanced our understanding of metal homeostasis and the roles that metals play in biology and medicine. Fluorescence-based metalloproteomics offers the possibility of not only visualization but also identification of metal-binding proteins in living cells and tissues. Herein, we summarize different strategies of labeling and tracking of metal-binding proteins with the aid of fluorescent probes. We highlight several examples as showcases of how this fluorescence-based metalloproteomics approach could be utilized in metallobiology and chemical biology. In conclusion, we also discuss the advantages and limitations of fluorescence-based metalloproteomics approaches and point out future directions of metalloproteomics including development of more sensitive and selective fluorescence probes, integration with other omics approaches, as well as application of emerging advanced super-resolution imaging techniques that utilize fluorescent molecules or proteins. We aim to attract more scientists to engage in this exciting field.