PDZ Domains in Microorganisms: Link Between Stress Response and Protein Synthesis

Abstract

The PSD-95/Dlg-A/ZO-1 (PDZ) domain is highly expanded and diversified in metazoan where it is known to assemble diverse signalling components by virtue of interactions with other proteins in sequence-specific manner. In contrast, in bacteria it monitors protein quality control during stress response. The distribution, functions and origin of PDZ domain-containing proteins in prokaryotes are largely unknown. We analyzed 7,852 PDZ domain-containing proteins in 1,474 prokaryotes and fungi. PDZ domains are abundant in eubacteria; and, this study confirms their occurrence also in archaea and fungi. Of all eubacterial PDZ domain-containing proteins, 89% are predicted to be membrane and periplasmic, explaining the depletion of bacterial domain forms in metazoan. Planctomycetes, myxobacteria and other eubacteria occupying terrestrial and aquatic niches encode more domain copies, which may have contributed towards multi-cellularity and prokaryotic-eukaryotic transition. Over 93% of the 7,852 PDZ-containing proteins classified into 12 families including 6 novel families. Out of these 88% harbour eight different protease domains, suggesting their substrate-specificity is guided by PDZ domains. The genomic context provides tantalizing insight towards the functions associated with PDZ domains and reinforces their involvement in protein synthesis. We propose that the highly variable PDZ domain of the uncharacterized Fe-S oxidoreductase superfamily, exclusively found in gladobacteria and several anaerobes and acetogens, may have preceded all existing PDZ domains.