The art of destruction: Revealing the proteolytic capacity of bacterial caspase homologs

Abstract

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 MolecularMicrobiology, 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 aeruginosaPCC 7806 in Escherichiacoli, 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. Bacterial caspase homologs are putative proteases with evolutionary connections to eukaryotic genetically controlled cell death programs. Klemenčič et al. have, for the first time, exposed the biochemical properties of one of these proteins, specifically the cyanobacterial caspase homolog MaOC1. The demonstrated proteolytic capability and activation mechanism of this caspase-like protein carries important implications for further studies in this relatively uncharted field.