Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking

Transition metals function as structural and catalytic cofactors for a large diversity of proteins and enzymes that collectively comprise the metalloproteome. Metallostasis considers all cellular processes, notably metal sensing, metalloproteome remodeling, and trafficking (or allocation) of metals that collectively ensure the functional integrity and adaptability of the metalloproteome. Bacteria employ both protein and RNA-based mechanisms that sense intracellular transition metal bioavailability and orchestrate systems-level outputs that maintain metallostasis. In this review, we contextualize metallostasis by briefly discussing the metalloproteome and specialized roles that metals play in biology. We then offer a comprehensive perspective on the diversity of metalloregulatory proteins and metal-sensing riboswitches, defining general principles within each sensor superfamily that capture how specificity is encoded in the sequence, and how selectivity can be leveraged in downstream synthetic biology and biotechnology applications. This is followed by a discussion of recent work that highlights selected metalloregulatory outputs, including metalloproteome remodeling and metal allocation by metallochaperones to both client proteins and compartments. We close by briefly discussing places where more work is needed to fill in gaps in our understanding of metallostasis.