Comparison of four different crystal forms of the<i>Mycobacterium tuberculosis</i>ESX-1 secreted protein regulator EspR

Gangwar, S.P.; Meena, Sita R.; Saxena, Ajay K.

doi:10.1107/s2053230x14004166

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…The CapH CTD homodimer is stabilized by a hydrophobic core comprising Phe81, Tyr85, Leu96, and Leu100 of each protomer (Fig 3C). The CapH CTD homodimer resembles the C‐terminal dimerization domains of other dimeric bacterial transcription factors, including Mycobacterium tuberculosis EspR, Bacillus subtilis SinR, and Citrobacter C.Csp231I (Lewis et al , 1998; Gangwar et al , 2014; Shevtsov et al , 2015). The CapH CTD homotetramer is assembled through a separate hydrophobic interface between the C‐terminal α‐helices of four protomers, involving residues Ile99 and Phe103 (Fig 3C).…”

Section: Resultsmentioning

confidence: 99%

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage

Lau

Enüstün

et al. 2022

The EMBO Journal

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To protect themselves from the constant threat of bacteriophage (phage) infection, bacteria have evolved diverse immune systems including restriction/modification, CRISPR/Cas, and many others. Here we describe the discovery of a two-protein transcriptional regulator module associated with hundreds of CBASS (Cyclic oligonucleotide Based Anti-phage Signaling System) immune systems, and demonstrate that this module drives expression of its associated CBASS system in response to DNA damage. We show that the helix-turn-helix transcriptional repressor CapH binds the promoter region of its associated CBASS system to repress transcription until it is cleaved by the metallopeptidase CapP. CapP is inactive except in the presence of singlestranded DNA, and CapP activity in cells is stimulated by DNA-damaging drugs. Together, CapH and CapP drive increased expression of their associated CBASS system in response to DNA damage. In both their structures and mechanisms, CapH and CapP resemble regulators that drive increased expression of DNA damage response genes in radiation-resistant Deinococcus, and control the mobilization of prophages and mobile elements in response to DNA damage. We also identify CapH and CapP-related proteins associated with diverse known and putative bacterial immune systems, including DISARM and two uncharacterized operons encoding proteins related to eukaryotic ubiquitin signaling pathways. Overall, our data highlight a mechanism by which bacterial immune systems can sense and respond to a universal stress signal, potentially enabling multiple immune systems to mount a coordinated defensive effort against an invading pathogen.

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Section: Resultsmentioning

confidence: 99%

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage

Lau

Enüstün

et al. 2022

The EMBO Journal

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“…2, Table S2), for it applies to the mycobacterial regulators KmsR (Campbell et al, 2007), ArgP (Zhou et al, 2010), BlaI (Sala et al, 2009) and EspR (Gangwar et al, 2014), which have all independently been confirmed to form homodimers in vitro.…”

Section: Distinguishing Monomeric From Dimeric Regulators In M Tubermentioning

confidence: 99%

Genome-wide characterization of monomeric transcriptional regulators in Mycobacterium tuberculosis

et al. 2016

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Gene transcription catalysed by RNA polymerase is regulated by transcriptional regulators, which play central roles in the control of gene transcription in both eukaryotes and prokaryotes. In regulating gene transcription, many regulators form dimers that bind to DNA with repeated motifs. However, some regulators function as monomers, but their mechanisms of gene expression control are largely uncharacterized. Here we systematically characterized monomeric versus dimeric regulators in the tuberculosis causative agent Mycobacterium tuberculosis. Of the .160 transcriptional regulators annotated in M. tuberculosis, 154 transcriptional regulators were tested, 22 % probably act as monomers and most are annotated as hypothetical regulators. Notably, all members of the WhiB-like protein family are classified as monomers. To further investigate mechanisms of monomeric regulators, we analysed the actions of these WhiB proteins and found that the majority interact with the principal sigma factor s A , which is also a monomeric protein within the RNA polymerase holoenzyme. Taken together, our study for the first time globally classified monomeric regulators in M. tuberculosis and suggested a mechanism for monomeric regulators in controlling gene transcription through interacting with monomeric sigma factors.

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A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage

Lau

Enüstün

et al. 2022

Preprint

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To protect themselves from the constant threat of bacteriophage (phage) infection, bacteria have evolved diverse immune systems including restriction/modification, CRISPR/Cas, and many others. Here we describe the discovery of a two-protein transcriptional regulator module associated with hundreds of CBASS (Cyclic oligonucleotide Based Anti-phage Signaling System) immune systems, and demonstrate that this module drives expression of its associated CBASS system in response to DNA damage. We show that the helix-turn-helix transcriptional repressor CapH binds the promoter region of its associated CBASS system to repress transcription until it is cleaved by the metallopeptidase CapP. CapP is inactive except in the presence of single-stranded DNA, and CapP activity in cells is stimulated by DNA-damaging drugs. Together, CapH and CapP drive increased expression of their associated CBASS system in response to DNA damage. In both their structures and mechanisms, CapH and CapP resemble regulators that drive increased expression of DNA damage response genes in radiation-resistant Deinococcus, and control the mobilization of prophages and mobile elements in response to DNA damage. We also identify CapH and CapP-related proteins associated with diverse known and putative bacterial immune systems, including DISARM and two uncharacterized operons encoding proteins related to eukaryotic ubiquitin signaling pathways. Overall, our data highlight a mechanism by which bacterial immune systems can sense and respond to a universal stress signal, potentially enabling multiple immune systems to mount a coordinated defensive effort against an invading pathogen.

show abstract

Comparison of four different crystal forms of theMycobacterium tuberculosisESX-1 secreted protein regulator EspR

Cited by 3 publications

References 30 publications

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage

Genome-wide characterization of monomeric transcriptional regulators in Mycobacterium tuberculosis

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage

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