5u51: Difference between revisions
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==Structure of Francisella tularensis heterodimeric SspA (MglA-SspA) in complex with ppGpp== | |||
<StructureSection load='5u51' size='340' side='right' caption='[[5u51]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5u51]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U51 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U51 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=G4P:GUANOSINE-5,3-TETRAPHOSPHATE'>G4P</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u56|5u56]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u51 OCA], [http://pdbe.org/5u51 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u51 RCSB], [http://www.ebi.ac.uk/pdbsum/5u51 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u51 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, F. tularensis is classified as a category A bioweapon by the US government. F. tularensis virulence stems from genes encoded on the Francisella pathogenicity island (FPI). An unusual set of Francisella 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 Francisella 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 F. tularensis pathogenesis is controlled by a highly interconnected molecular circuitry in which the virulence machinery directly senses infection via a small molecule stress signal. | |||
Dissection of the molecular circuitry controlling virulence in Francisella tularensis.,Cuthbert BJ, Ross W, Rohlfing AE, Dove SL, Gourse RL, Brennan RG, Schumacher MA Genes Dev. 2017 Aug 1;31(15):1549-1560. doi: 10.1101/gad.303701.117. Epub 2017, Sep 1. PMID:28864445<ref>PMID:28864445</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Cuthbert, B | <div class="pdbe-citations 5u51" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Brennan, R G]] | |||
[[Category: Cuthbert, B J]] | |||
[[Category: Schumacher, M A]] | |||
[[Category: Gst-fold]] | |||
[[Category: Macrophage growth locus some]] | |||
[[Category: Ppgpp]] | |||
[[Category: Stringent starvation protein some]] | |||
[[Category: Transcription]] | |||
Revision as of 12:39, 27 September 2017
Structure of Francisella tularensis heterodimeric SspA (MglA-SspA) in complex with ppGppStructure of Francisella tularensis heterodimeric SspA (MglA-SspA) in complex with ppGpp
Structural highlights
Publication Abstract from PubMedFrancisella tularensis, the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, F. tularensis is classified as a category A bioweapon by the US government. F. tularensis virulence stems from genes encoded on the Francisella pathogenicity island (FPI). An unusual set of Francisella 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 Francisella 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 F. tularensis pathogenesis is controlled by a highly interconnected molecular circuitry in which the virulence machinery directly senses infection via a small molecule stress signal. Dissection of the molecular circuitry controlling virulence in Francisella tularensis.,Cuthbert BJ, Ross W, Rohlfing AE, Dove SL, Gourse RL, Brennan RG, Schumacher MA Genes Dev. 2017 Aug 1;31(15):1549-1560. doi: 10.1101/gad.303701.117. Epub 2017, Sep 1. PMID:28864445[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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