spoT

The stringent response regulated by SpoT, RelA, and their homologues can cause a bacterium to increase its persistence in stressful environments.{{cite journal | vauthors = Balaban NQ, Helaine S, Lewis K, Ackermann M, Aldridge B, Andersson DI, Brynildsen MP, Bumann D, Camilli A, Collins JJ, Dehio C, Fortune S, Ghigo JM, Hardt WD, Harms A, Heinemann M, Hung DT, Jenal U, Levin BR, Michiels J, Storz G, Tan MW, Tenson T, Van Melderen L, Zinkernagel A | display-authors = 6 | title = Definitions and guidelines for research on antibiotic persistence | journal = Nature Reviews. Microbiology | volume = 17 | issue = 7 | pages = 441–448 | date = July 2019 | pmid = 30980069 | pmc = 7136161 | doi = 10.1038/s41579-019-0196-3 }} SpoT can act as both a hydrolase and a synthetase to (p)ppGpp alarmones in the stringent response pathway with Mn2+ as its cofactor.{{Cite web |title=spoT - Bifunctional (p)ppGpp synthase/hydrolase SpoT - Escherichia coli (strain K12) - spoT gene & protein |url=https://www.uniprot.org/uniprot/P0AG24 |access-date=2022-05-01 |website=www.uniprot.org |language=en}} When there are environmental stressors present, SpoT uses ATP and GDP to synthesize (p)ppGpp and catalyze the stringent response.{{cite journal | vauthors = Ronneau S, Hallez R | title = Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria | journal = FEMS Microbiology Reviews | volume = 43 | issue = 4 | pages = 389–400 | date = July 2019 | pmid = 30980074 | pmc = 6606846 | doi = 10.1093/femsre/fuz009 }} When stressors are removed and a stringent response is no longer necessary SpoT hydrolyzes (p)ppGpp, cleaving it into GTP and diphosphate. Environmental stressors including but not limited to amino acid starvation, carbon deficiencies,{{cite journal | vauthors = Lesley JA, Shapiro L | title = SpoT regulates DnaA stability and initiation of DNA replication in carbon-starved Caulobacter crescentus | journal = Journal of Bacteriology | volume = 190 | issue = 20 | pages = 6867–6880 | date = October 2008 | pmid = 18723629 | pmc = 2566184 | doi = 10.1128/JB.00700-08 }} phosphate deficiencies{{cite journal | vauthors = Spira B, Silberstein N, Yagil E | title = Guanosine 3',5'-bispyrophosphate (ppGpp) synthesis in cells of Escherichia coli starved for Pi | journal = Journal of Bacteriology | volume = 177 | issue = 14 | pages = 4053–4058 | date = July 1995 | pmid = 7608079 | pmc = 177136 | doi = 10.1128/jb.177.14.4053-4058.1995 }} and changes in temperature have been documented to cause the gene encoding SpoT to activate.

The acyl carrier protein (ACP) binds to the TGS domain of SpoT; this binding is probably influenced by the ratio of unacylated ACP to acylated ACP in the cell.{{cite journal | vauthors = Battesti A, Bouveret E | title = Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolism | journal = Molecular Microbiology | volume = 62 | issue = 4 | pages = 1048–1063 | date = November 2006 | pmid = 17078815 | doi = 10.1111/j.1365-2958.2006.05442.x | s2cid = 7857443 | doi-access = free }}

SpoT mainly serves as a hydrolase in systems similar to E.coli. SpoT's hydrolase activity is Mn2+-dependent with a conserved His-Asp (HD) motif.{{cite journal | vauthors = Yakunin AF, Proudfoot M, Kuznetsova E, Savchenko A, Brown G, Arrowsmith CH, Edwards AM | title = The HD domain of the Escherichia coli tRNA nucleotidyltransferase has 2',3'-cyclic phosphodiesterase, 2'-nucleotidase, and phosphatase activities | journal = The Journal of Biological Chemistry | volume = 279 | issue = 35 | pages = 36819–36827 | date = August 2004 | pmid = 15210699 | doi = 10.1074/jbc.M405120200 | doi-access = free }} Phosphate starvation is sensed by SpoT hydrolase to elevate (p)ppGpp, which induces IraP, a RssB antiadaptor that antagonizes RssB activation of RpoS turnover, thereby inducing RpoS.

In E. coli, the SpoT protein consists of 702 amino acids. E.coli uses RelA and SpoT as its two main (p)ppGpp regulating enzymes.{{cite journal | vauthors = Liu K, Bittner AN, Wang JD | title = Diversity in (p)ppGpp metabolism and effectors | journal = Current Opinion in Microbiology | volume = 24 | pages = 72–79 | date = April 2015 | pmid = 25636134 | pmc = 4380541 | doi = 10.1016/j.mib.2015.01.012 | series = Cell regulation }} When the gene for encoding RelA is nonfunctional, E. coli can still regulate (p)ppGpp through SpoT as it has both HD and SYNTH domains.

File:Pone.0023479.g001.png

SpoT and RelA have many homologous variations, forming the RelA/SpoT Homologue (RSH) protein family. These homologues serve similar functions to SpoT and RelA in stringent responses. Protein domains observed in members of the RSH protein family are separated by hydrolase (HD) functionality and synthetase (SYNTH) functionality (see Figure 2).

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• {{cite journal | vauthors = Srivatsan A, Wang JD | title = Control of bacterial transcription, translation and replication by (p)ppGpp | journal = Current Opinion in Microbiology | volume = 11 | issue = 2 | pages = 100–5 | date = April 2008 | pmid = 18359660 | doi = 10.1016/j.mib.2008.02.001 }}
• {{cite journal | vauthors = Wendrich TM, Marahiel MA | title = Cloning and characterization of a relA/spoT homologue from Bacillus subtilis | journal = Molecular Microbiology | volume = 26 | issue = 1 | pages = 65–79 | date = October 1997 | pmid = 9383190 | doi = 10.1046/j.1365-2958.1997.5511919.x | s2cid = 33335651 | doi-access = free }}

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Category:Bacterial proteins