Metal trafficking in the cell: Combining atomic resolution with cellular dimension

Metals are widely present in biological systems as simple ions or complex cofactors, and are involved in a variety of processes essential for life. Their transport inside cells and insertion into the binding sites of the proteins that need metals to function occur through complex and selective pathways involving dedicated multiprotein machineries specifically and transiently interacting with each other, often sharing the coordination of metal ions and/or cofactors. The understanding of these machineries requires integrated approaches, ranging from bioinformatics to experimental investigations, possibly in the cellular context. In this review, we report two case studies where the use of integrated in vitro and in cellulo approaches is necessary to clarify at atomic resolution essential aspects of metal trafficking in cells.