Stringent response

Response

In Escherichia coli, (p)ppGpp production is mediated by the ribosomal protein L11 (rplK resp. relC) and the ribosome-associated (p)ppGpp synthetase I, RelA; deacylated tRNA bound in the ribosomal A-site is the primary induction signal. RelA converts GTP and ATP into pppGpp by adding the pyrophosphate from ATP onto the 3' carbon of the ribose in GTP, releasing AMP. pppGpp is converted to ppGpp by the gpp gene product, releasing Pi. ppGpp is converted to GDP by the spoT gene product, releasing pyrophosphate (PPi). GDP is converted to GTP by the ndk gene product. Nucleoside triphosphate (NTP) provides the Pi, and is converted to Nucleoside diphosphate (NDP).

In other bacteria, the stringent response is mediated by a variety of RelA/SpoT Homologue (RSH) proteins, with some having only synthetic, or hydrolytic or both (Rel) activities.

During the stringent response, (p)ppGpp accumulation affects the resource-consuming cell processes replication, transcription, and translation. (p)ppGpp is thought to bind RNA polymerase and alter the transcriptional profile, decreasing the synthesis of translational machinery (such as rRNA and tRNA), and increasing the transcription of biosynthetic genes. Additionally, the initiation of new rounds of replication is inhibited and the cell cycle arrests until nutrient conditions improve. Translational GTPases involved in protein biosynthesis are also affected by ppGpp, with Initiation Factor 2 (IF2) being the main target.

Chemical reaction catalyzed by RelA:

: ATP + GTP → AMP + pppGpp

Chemical reaction catalyzed by SpoT:

: ppGpp → GDP + PPi

or

: pppGpp - GTP + PPi

References

References

1. (July 2024). "Microbial Primer: What is the stringent response and how does it allow bacteria to survive stress?". Microbiology.
2. (1973). "Synthesis of guanosine tetra- and pentaphosphate requires the presence of a codon-specific, uncharged transfer ribonucleic acid in the acceptor site of ribosomes". Proc Natl Acad Sci U S A.
3. (2006). "Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolism". Molecular Microbiology.
4. (2005). "Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli". Molecular Microbiology.
5. (1977). "Anomalous synthesis of ppGpp in growing cells". Cell.
6. (May 2023). "Localization and expression of CRSH transcript, level of calcium ions, and cell cycle activity during Brassica napus L. seed development". Industrial Crops and Products.
7. (2011). "The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life.". PLOS ONE.
8. (2008). "(p)ppGpp: still magical?". Annu Rev Microbiol.
9. (2008). "The global, ppGpp-mediated stringent response to amino acid starvation in Escherichia coli.". Molecular Microbiology.
10. (2008). "Control of bacterial transcription, translation and replication by (p)ppGpp.". Current Opinion in Microbiology.
11. (2010). "Thermodynamic characterization of ppGpp binding to EF-G or IF2 and of initiator tRNA binding to free IF2 in the presence of GDP, GTP, or ppGpp.". Journal of Molecular Biology.