PDZ Domains in Microorganisms: Link between Stress Response

10 Abstract The PSD-95/Dlg-A/ZO-1 (PDZ) domain is highly expanded and diversified in 11 metazoan where it is known to assemble diverse signalling components by virtue of interactions 12 with other proteins in sequence-specific manner. In contrast, in bacteria it monitors protein 13 quality control during stress response. The distribution, functions and origin of PDZ domain14 containing proteins in prokaryotes are largely unknown. We analyzed 7,852 PDZ domain15 containing proteins in 1,474 prokaryotes and fungi. PDZ domains are abundant in eubacteria; 16 and, this study confirms their occurrence also in archaea and fungi. Of all eubacterial PDZ 17 domain-containing proteins, 89% are predicted to be membrane and periplasmic, explaining the 18 depletion of bacterial domain forms in metazoan. Planctomycetes, myxobacteria and other 19 eubacteria occupying terrestrial and aquatic niches encode more domain copies, which may 20 have contributed towards multi-cellularity and prokaryotic-eukaryotic transition. Over 93% of 21 the 7,852 PDZ-containing proteins classified into 12 families including 6 novel families. Out of 22 these 88% harbour eight different protease domains, suggesting their substrate-specificity is 23 guided by PDZ domains. The genomic context provides tantalizing insight towards the functions 24 associated with PDZ domains and reinforces their involvement in protein synthesis. We propose 25 that the highly variable PDZ domain of the uncharacterized Fe-S oxidoreductase superfamily, 26 exclusively found in gladobacteria and several anaerobes and acetogens, may have preceded all 27 existing PDZ domains. 28 29