Function
Stringent starvation protein A (SspA) is an RNA polymerase-associated protein involved in nucleotide metabolism, acid tolerance[1] and virulence of bacteria[2].
In Francisella virulence, a set of regulators are essensial for its activation. These regulators include the heterodimer of SspA, macrophage growth locus A (MglA) and pathogenicity island gene regulator (PigR). The guanosine-tetraphosphate (ppGpp) is also involved in coordinating the virulence. Stringent starvation protein B (SspB) binds to residues in the tag of tmRNA proteins marking them for degradation [3].
Relevance
Tularemia caused by the pathogen Francisella tularensis may be treated by inhibitors of SspA-MglA regulators[4].
Structural highlights
The 3D structure of the complex of SspA and MglA shows a heterodimer with favourable interactions between the two molecules[5]. The ppGpp molecule binds to the open face of the SspA-MglA heterodimer interacting with both molecules
3D structures of stringent starvation protein
Stringent starvation protein 3D structures
- ↑ Hansen AM, Qiu Y, Yeh N, Blattner FR, Durfee T, Jin DJ. SspA is required for acid resistance in stationary phase by downregulation of H-NS in Escherichia coli. Mol Microbiol. 2005 May;56(3):719-34. doi: 10.1111/j.1365-2958.2005.04567.x. PMID:15819627 doi:https://dx.doi.org/10.1111/j.1365-2958.2005.04567.x
- ↑ Wang F, Shi J, He D, Tong B, Zhang C, Wen A, Zhang Y, Feng Y, Lin W. Structural basis for transcription inhibition by E. coli SspA. Nucleic Acids Res. 2020 Sep 25;48(17):9931-9942. doi: 10.1093/nar/gkaa672. PMID:32785630 doi:https://dx.doi.org/10.1093/nar/gkaa672
- ↑ Flynn JM, Levchenko I, Seidel M, Wickner SH, Sauer RT, Baker TA. Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10584-9. doi:, 10.1073/pnas.191375298. Epub 2001 Sep 4. PMID:11535833 doi:https://dx.doi.org/10.1073/pnas.191375298
- ↑ Ma Z, King K, Alqahtani M, Worden M, Muthuraman P, Cioffi CL, Bakshi CS, Malik M. Stringent response governs the oxidative stress resistance and virulence of Francisella tularensis. PLoS One. 2019 Oct 24;14(10):e0224094. doi: 10.1371/journal.pone.0224094., eCollection 2019. PMID:31648246 doi:https://dx.doi.org/10.1371/journal.pone.0224094
- ↑ Cuthbert BJ, Ross W, Rohlfing AE, Dove SL, Gourse RL, Brennan RG, Schumacher MA. Dissection of the molecular circuitry controlling virulence in Francisella tularensis. Genes Dev. 2017 Aug 1;31(15):1549-1560. doi: 10.1101/gad.303701.117. Epub 2017, Sep 1. PMID:28864445 doi:https://dx.doi.org/10.1101/gad.303701.117
