The art of destruction: revealing the proteolytic capacity of bacterial caspase homologs.

Caspases are proteases that initiate and execute programmed cell death in animal tissues, thereby facilitating multicellular development and survival. While caspases are unique to metazoans and specifically cleave substrates at aspartic acid residues, homologs are found in protozoa, plants, algae, fungi, bacteria and archaea, and show specificity for basic residues. In this issue of Molecular Microbiology, Klemenčič and colleagues present the first biochemical characterization of a bacterial caspase homolog, classified as an orthocaspase. By expressing the gene MaOC1 from the cyanobacterium Microcystis aeruginosa PCC 7806 in Escherichia coli, the authors discovered specificity for substrates with arginine in the P1 position. The protein requires autocatalytic processing to become active and is dependent on an intact histidine-cysteine dyad. These results significantly extend our knowledge of the specificities of bacterial caspase homologs, which are known to be highly diverse in protein domain architectures and active site mutations. Although bacterial programmed cell death is one possible area of action, the function of most bacterial caspase homologs remains unexplored. Cyanobacteria represent the best studied group in terms of prokaryotic caspase-like proteins both genomically and experimentally, and thereby provide a suitable platform for further investigations into activation, regulation and physiological roles of orthocaspases.