3r1f

Crystal structure of a key regulator of virulence in Mycobacterium tuberculosis

spinqualitylabelsall models 3r1f, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3r1f is a 18 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed EspR is a transcriptional regulator that activates the ESX-1 secretion system during Mycobacterium tuberculosis infection and is critical for pathogenesis. It is unique among DNA-binding proteins as it is secreted as part of a feedback regulatory loop that serves to mitigate transcriptional activity. Here we report the crystal structure of a functional EspR dimer at 2.5-A resolution. The amino-terminal half of EspR is a helix-turn-helix (HTH) DNA-binding domain and the carboxy terminus consists of a dimerization domain with similarity to the SinR:SinI sporulation regulator of Bacillus subtilis. Surprisingly, the HTH domains of EspR are arranged in an unusual conformation in which they are splayed at an oblique angle to each other, suggesting that EspR binds DNA in a profoundly different way than most other known HTH regulators. By mapping the EspR binding sites in the espACD promoter, using both in vivo and in vitro binding assays, we show that the EspR operators are located unusually far from the promoter. The EspR dimer binds to these sites cooperatively, but the two "half-sites" contacted by each DNA recognition motif are separated by 177 base pairs. The distinctive structure of EspR and the exceptional arrangement of its operator contacts suggest that it could promote DNA looping in its target promoter. We hypothesize that direct DNA looping mediated by single-site binding of each EspR monomer may facilitate transcriptional control of this important virulence system. EspR, a key regulator of Mycobacterium tuberculosis virulence, adopts a unique dimeric structure among helix-turn-helix proteins.,Rosenberg OS, Dovey C, Tempesta M, Robbins RA, Finer-Moore JS, Stroud RM, Cox JS Proc Natl Acad Sci U S A. 2011 Jul 27. PMID:21795602 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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