The stringent response, also called stringent control, is a stress response of bacteria and plant chloroplasts in reaction to amino-acid starvation, fatty acid limitation, iron limitation, heat shock and other stress conditions. The stringent response is signaled by the alarmone (p)ppGpp, and modulates transcription of up to 1/3 of all genes in the cell. This in turn causes the cell to divert resources away from growth and division and toward amino acid synthesis in order to promote survival until nutrient conditions improve.
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).
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
Extensive Mendeley collection of scientific papers covering stringent response is available here.
- W Haseltine; R Block (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. 70 (5): 1564–1568. doi:10.1073/pnas.70.5.1564. PMC . PMID 4576025.
- A Battesti; E Bouveret (2006). "Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolism". Molecular Microbiology. 62 (4): 1048–1063. doi:10.1111/j.1365-2958.2006.05442.x. PMID 17078815.
- D Vinella; C Albrecht; M Cashel; R D'Ari (2005). "Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli". Molecular Microbiology. 56 (4): 958–970. doi:10.1111/j.1365-2958.2005.04601.x. PMID 15853883.
- J Gallant; L Palmer; C C Pao (1977). "Anomalous synthesis of ppGpp in growing cells". Cell. 11 (1): 181–185. doi:10.1016/0092-8674(77)90329-4. PMID 326415.
- Atkinson GC, Tenson T, Hauryliuk V (2011). "The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life.". PLoS ONE. 6 (8): e23479. doi:10.1371/journal.pone.0023479. PMC . PMID 21858139.
- K Potrykus; M Cashel (2008). "(p)ppGpp: still magical?". Annu Rev Microbiol. 62: 35–51. doi:10.1146/annurev.micro.62.081307.162903. PMID 18454629.
- Traxler MF, Summers SM, Nguyen HT, Zacharia VM, Hightower GA, Smith JT, Conway T (2008). "The global, ppGpp-mediated stringent response to amino acid starvation in Escherichia coli.". Molecular Microbiology. 68 (5): 1128–48. doi:10.1111/j.1365-2958.2008.06229.x. PMID 18430135.
- Srivatsan A, Wang JD (2008). "Control of bacterial transcription, translation and replication by (p)ppGpp.". Current Opinion in Microbiology. 11 (2): 100–105. doi:10.1016/j.mib.2008.02.001. PMID 18359660.
- Mitkevich VA, Ermakov A, Kulikova AA, Tankov S, Shyp V, Soosaar A, Tenson T, Makarov AA, Ehrenberg M, Hauryliuk V (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. 402 (5): 838–846. doi:10.1016/j.jmb.2010.08.016. PMID 20713063.