6ALX
Structure of F. tularensis MglA-SspA solved in the presence of polyP
Summary for 6ALX
| Entry DOI | 10.2210/pdb6alx/pdb |
| Related | 5U51 5U56 |
| Descriptor | Stringent starvation protein A, Macrophage growth locus A (2 entities in total) |
| Functional Keywords | mgla, sspa, francisella tularensis, bioweapon, ppgpp, transcription |
| Biological source | Francisella tularensis More |
| Total number of polymer chains | 4 |
| Total formula weight | 95409.25 |
| Authors | Schumacher, M.A. (deposition date: 2017-08-08, release date: 2017-08-23, Last modification date: 2023-10-04) |
| Primary citation | Cuthbert, B.J.,Ross, W.,Rohlfing, A.E.,Dove, S.L.,Gourse, R.L.,Brennan, R.G.,Schumacher, M.A. Dissection of the molecular circuitry controlling virulence in Francisella tularensis. Genes Dev., 31:1549-1560, 2017 Cited by PubMed Abstract: the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, is classified as a category A bioweapon by the US government. virulence stems from genes encoded on the pathogenicity island (FPI). An unusual set of regulators-the heteromeric macrophage growth locus protein A (MglA)-stringent starvation protein A (SspA) complex and the DNA-binding protein pathogenicity island gene regulator (PigR)-activates FPI transcription and thus is essential for virulence. Intriguingly, the second messenger, guanosine-tetraphosphate (ppGpp), which is produced during infection, is also involved in coordinating virulence; however, its role has been unclear. Here we identify MglA-SspA as a novel ppGpp-binding complex and describe structures of apo- and ppGpp-bound MglA-SspA. We demonstrate that MglA-SspA, which binds RNA polymerase (RNAP), also interacts with the C-terminal domain of PigR, thus anchoring the (MglA-SspA)-RNAP complex to the FPI promoter. Furthermore, we show that MglA-SspA must be bound to ppGpp to mediate high-affinity interactions with PigR. Thus, these studies unveil a novel pathway different from those described previously for regulation of transcription by ppGpp. The data also indicate that pathogenesis is controlled by a highly interconnected molecular circuitry in which the virulence machinery directly senses infection via a small molecule stress signal. PubMed: 28864445DOI: 10.1101/gad.303701.117 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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