InterPro domain: IPR033655

The RelA (SpoT) protein, also referred to as ppGpp hydrolase/synthetase, is a ribosome-associated protein that is activated during amino acid starvation and thought to mediate the stringent response. RelA contains a TGS domain, named after the Threonyl-tRNA Synthetase, GTPase, and SpoT proteins where it occurs [ 1 ]. This domain of RelA binds the CCA tail to orient the free 3' hydroxyl group of the terminal adenosine towards a beta-strand, thus an aminoacylated tRNA at this position would be sterically impeded. This association suppresses auto-inhibition and activates the synthesis of (p)ppGpp and initiates the stringent response. [ 2 , 3 ].

1. The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life. PLoS ONE 6, e23479
2. Ribosome-dependent activation of stringent control. Nature 534
3. Ribosome•RelA structures reveal the mechanism of stringent response activation. Elife 5, 277-280