PDZ Domains across the microbial world: Molecular Link to the Proteases, Stress Response and Protein Synthesis

Abstract

The PSD-95/Dlg-A/ZO-1 (PDZ) domain is highly expanded, diversified and well distributed across the metazoa where it assembles diverse signalling components by virtue of interactions with other proteins in a sequence-specific manner. In contrast, in the microbial world they are reported to be involved in protein quality control during stress response. The distribution, functions, and origins of PDZ domain-containing proteins in the prokaryotic organisms remain largely unexplored. We analysed 7,852 PDZ domain-containing proteins in 1,474 microbial genomes in this context. PDZ domain-containing proteins from planctomycetes, myxobacteria and other eubacteria occupying terrestrial and aquatic niches are found to be in multiple copies within their genomes. Over 93% of the 7,852 PDZ-containing proteins were classified into 12 families including 6 novel families based on additional structural and functional domains present in these proteins. The higher PDZ domain encoding capacity of the investigated organisms was observed to be associated with adaptation to the ecological niche where multicellular life might have originated and flourished. Predicted subcellular localization of PDZ domain-containing proteins and their genomic context argue in favour of crucial roles in translation and membrane remodelling during stress response. Based on rigorous sequence, structure and phylogenetic analyses, we propose that the highly diverse PDZ domain of the uncharacterized Fe-S oxidoreductase superfamily, exclusively found in gladobacteria and several anaerobes and acetogens, might represent the most ancient form among all of the existing PDZ domains.