| Structural highlights
Function
[ESPR_MYCTU] Virulence regulator that has both architectural and regulatory roles. Impacts cell wall functions and pathogenesis through regulation of multiple genes, including the espACD operon, which is a key ESX-1 component. Influences target gene expression positively or negatively, depending on its binding position relative to the genes it controls. Acts by binding directly to the DNA. May play a central role in regulating virulence gene expression.[1] [2] [3] [4]
Publication Abstract from PubMed
The human pathogen Mycobacterium tuberculosis requires the ESX-1 secretion system for full virulence. EspR plays a key role in ESX-1 regulation via direct binding and transcriptional activation of the espACD operon. Here, we describe the crystal structures of EspR, a C-terminally truncated form, EspRDelta10, as well as an EspR-DNA complex. EspR forms a dimer with each monomer containing an N-terminal helix-turn-helix DNA binding motif and an atypical C-terminal dimerization domain. Structural studies combined with footprinting experiments, atomic force microscopy and molecular dynamic simulations allow us to propose a model in which a dimer of EspR dimers is the minimal functional unit with two subunits binding two consecutive major grooves. The other two DNA binding domains are thus free to form higher-order oligomers and to bridge distant DNA sites in a cooperative way. These features are reminiscent of nucleoid-associated proteins and suggest a more general regulatory role for EspR than was previously suspected.
Atypical DNA recognition mechanism used by the EspR virulence regulator of Mycobacterium tuberculosis.,Blasco B, Stenta M, Alonso-Sarduy L, Dietler G, Peraro MD, Cole ST, Pojer F Mol Microbiol. 2011 Aug 30. doi: 10.1111/j.1365-2958.2011.07813.x. PMID:21883526[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Raghavan S, Manzanillo P, Chan K, Dovey C, Cox JS. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature. 2008 Aug 7;454(7205):717-21. doi: 10.1038/nature07219. PMID:18685700 doi:http://dx.doi.org/10.1038/nature07219
- ↑ Hunt DM, Sweeney NP, Mori L, Whalan RH, Comas I, Norman L, Cortes T, Arnvig KB, Davis EO, Stapleton MR, Green J, Buxton RS. Long-range transcriptional control of an operon necessary for virulence-critical ESX-1 secretion in Mycobacterium tuberculosis. J Bacteriol. 2012 May;194(9):2307-20. doi: 10.1128/JB.00142-12. Epub 2012 Mar 2. PMID:22389481 doi:http://dx.doi.org/10.1128/JB.00142-12
- ↑ Blasco B, Chen JM, Hartkoorn R, Sala C, Uplekar S, Rougemont J, Pojer F, Cole ST. Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein. PLoS Pathog. 2012;8(3):e1002621. doi: 10.1371/journal.ppat.1002621. Epub 2012 Mar, 29. PMID:22479184 doi:http://dx.doi.org/10.1371/journal.ppat.1002621
- ↑ Blasco B, Stenta M, Alonso-Sarduy L, Dietler G, Peraro MD, Cole ST, Pojer F. Atypical DNA recognition mechanism used by the EspR virulence regulator of Mycobacterium tuberculosis. Mol Microbiol. 2011 Aug 30. doi: 10.1111/j.1365-2958.2011.07813.x. PMID:21883526 doi:10.1111/j.1365-2958.2011.07813.x
- ↑ Blasco B, Stenta M, Alonso-Sarduy L, Dietler G, Peraro MD, Cole ST, Pojer F. Atypical DNA recognition mechanism used by the EspR virulence regulator of Mycobacterium tuberculosis. Mol Microbiol. 2011 Aug 30. doi: 10.1111/j.1365-2958.2011.07813.x. PMID:21883526 doi:10.1111/j.1365-2958.2011.07813.x
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