The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life.

摘要: RelA/SpoT Homologue (RSH) proteins, named for their sequence similarity to the RelA and SpoT enzymes of Escherichia coli, comprise a superfamily that synthesize and/or hydrolyze alarmone ppGpp, activator “stringent” response regulator cellular metabolism. The classical “long” RSHs Rel, with ppGpp hydrolase, synthetase, TGS ACT domain architecture have been found across diverse bacteria plant chloroplasts, while dedicated single ppGpp-synthesizing -hydrolyzing also discovered in disparate animals respectively. However, there is considerable confusion terms nomenclature no comprehensive phylogenetic analyses previously carried out classify on genomic scale. We performed high-throughput sensitive searching over 1000 genomes from tree life, combination consolidate previous ad hoc identification different organisms provide much-needed unifying terminology field. into 30 subgroups comprising three groups: long RSHs, small synthetases (SASs), hydrolases (SAHs). Members nineteen unidentified RSH can now be studied experimentally, including unknown archaea, expanding “stringent response” this life. analyzed possible combinations proteins domains bacterial compared content available knock-out data various determine rules combining RSHs. Through comparative analysis we find exposed sites limited conservation propose are involved transmitting regulatory signals. Such signals may transmitted via NTD CTD intra-molecular interactions, or inter-molecular interactions either among individual molecules other binding partners such as ribosome.