Wednesday, August 10, 2011

The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life

Stringent response is run by the RSH (RelA / SpoT Homologue) proteins, but there are more RSHs then just these two. Usually researchers were finding them using an ad hoc approach: take your favorite bug you worked with for 10 years, blast its genome with RelA gene, find anything that looks like RelA, test  it.

Finally there is a proper analysis of RSHs across the tree of life: The RelA/SpoT Homolog superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life by Atkinson GC, Tenson T, Hauryliuk V, PLoS ONE, 6(8): e23479. 

Here is the take home message:
  • there are loads of different RSHs out there: we identified 30 subgroups! 
  • all the RSHs out there are now are classified (for now, that is. New genomes are coming out every day, damn the progress!).
  • Archaea, Bacteria, Eucaryotes: they all have RSHs. I repeat: Archaea too.
  • there are the long RSHs (i.e. Rel, RelA and SpoT) and there are the short ones. 
  • The short ones have either ppGpp synthesis or ppGpp hydrolysis domain. The long ones have both, but not always both are functional.
  • by comparing the long ones vs the short ones we identified residues potentially involved in the inter-domain cross-talk in the long ones (the short ones have only one domain thus there is no cross talk there!).
The bottom line: if you work on a strange RSH protein from a strange bug, do check out our paper. 
Fig. 1.  Maximum likelihood phylogeny of the ppGpp hydrolase domain.  Subgroups are labeled and shading behind the branches shows the most common domain structure observed for those groups, as per the legend in the inset box. Symbols on branches indicate bootstrap support, as per the inset box.

Hurray to Gem


  1. Hello!

    Its has been a wile since Ive started to read your blog! I find it very interesting. Every time I check it out I find something new about the stringent response :). Something Im wondering is if you know what are the actual concentration of ppGpp in the cells upon entry in the stationary face, because I have always seen only the ratio between ppGpp/GTP. I hope you can help me,Thank you!

    It woud be great if you can give me the name of a paper. bye.

  2. Hi!

    It is quite tricky to measure the concentration of ppGpp in the cell - ppGpp losses during the sample preparation is one problem, unknown volume of the cells used for preparing the sample is another one.

    The best paper is this one:

    They do try to recalculate the ratios into the actual concentrations of ppGpp. Naturally, several assumptions are made (cell volume, etc.). In general the estimates range from 100 uM to 1 mM.

  3. I am wondering if you have a good resource for common binding sites for these transcription factors. I am looking at the regulation of lipids (DXP pathway) in bacteria. It seems that the dxs gene is down regulated by RelA, but I would like to know the putative binding site for the transcription factor if it is published. Thank you.