Abstract
The PSD-95/Dlg-A/ZO-1 (PDZ) domain is highly expanded, diversified, and well distributed across metazoa where it assembles diverse signaling 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 analyzed 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 domain-containing proteins were classified into 12 families including six 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 favor of crucial roles in translation and membrane remodeling 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 the existing PDZ domains.
Highlights
Proteins displaying both signaling and protein–protein interaction domains are prevalent in eukaryotic signal transduction systems (Nourry et al 2003)
We identified 7,852 proteins in 1,419 of 1,474 (96%) analyzed genomes with 9,975 significant hits to the PDZ domain Hidden Markov models (HMMs) obtained from the Pfam and Superfamily databases
PDZ domains were found absent in 4% of species (55 genomes), mainly belonging to cell-wall lacking mollicute and candidate phytoplasma species, of which many are adapted to a parasitic lifestyle
Summary
Proteins displaying both signaling and protein–protein interaction domains are prevalent in eukaryotic signal transduction systems (Nourry et al 2003). The PDZ domain is one of such protein–protein interaction domains. It was first identified in the context of signaling proteins, which are referred to as GLGF repeats proteins or DHR (discs large homology repeat) proteins (Cho et al 1992; Ponting and Phillips 1995). Metazoan PDZ domains referred to as the canonical PDZ domains typically comprise 80–100 amino acid residues harboring a highly conserved fold (Kennedy 1995; Doyle et al 1996). The eubacterial PDZ domains fold to the metazoan domains but with a distinct topology of secondary structural elements and are referred to as noncanonical (Harris and Lim 2001; Lee and Zheng 2010). All PDZ domains exhibit diversity in their functional roles and binding specificities (Sakarya et al 2010; Belotti et al 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
