Characterization of Mycobacterium tuberculosis WhiB1/Rv3219 as a protein disulfide reductase

Garg, Saurabh; Alam, Suhail; Soni, Vishal; Kishan, K. V. Radha; Agrawal, Pushpa

doi:10.1016/j.pep.2006.10.015

Cited by 32 publications

(39 citation statements)

References 43 publications

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“…In mycobacteria, WhiB proteins are capable of binding redox-sensitive [4Fe-4S] clusters, which can serve as redox-active co-factors or as switches that reflect the reductive and oxidative potential of a cell[26]. The WhiB proteins may be disulfide reductases[27], but are certainly transcription factors capable of modulating cellular processes that are intimately tied to the redox state of the cell or perceived oxidative stress[28]. In Mtb, WhiB1 is an essential DNA binding protein capable of auto-repressing its own transcription[21].…”

Section: Discussionmentioning

confidence: 99%

Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis

et al. 2014

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Unlike most bacterial species, Mycobacterium tuberculosis depends on the Clp proteolysis system for survival even in in vitro conditions. We hypothesized that Clp is required for the physiologic turnover of mycobacterial proteins whose accumulation is deleterious to bacterial growth and survival. To identify cellular substrates, we employed quantitative proteomics and transcriptomics to identify the set of proteins that accumulated upon the loss of functional Clp protease. Among the set of potential Clp substrates uncovered, we were able to unambiguously identify WhiB1, an essential transcriptional repressor capable of auto-repression, as a substrate of the mycobacterial Clp protease. Dysregulation of WhiB1 turnover had a toxic effect that was not rescued by repression of whiB1 transcription. Thus, under normal growth conditions, Clp protease is the predominant regulatory check on the levels of potentially toxic cellular proteins. Our findings add to the growing evidence of how post-translational regulation plays a critical role in the regulation of bacterial physiology.

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Section: Discussionmentioning

confidence: 99%

Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis

et al. 2014

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“…It was shown that the WhiB3 protein from Mycobacterium tuberculosis interacted with the carboxyterminal domain of the principle RNA polymerase sigma factor in a yeast two-hybrid screening (Steyn et al, 2002), suggesting a function of WhiB3 as transcription regulator by indirect evidence, despite the lack of a typical DNA-binding domain. Later, it was demonstrated that WhiB proteins from M. tuberculosis (WhiB1 and WhiB4) contain redox-sensitive iron-sulfur clusters and can function as protein disulfide reductases Garg et al, 2007). However, it cannot be excluded at present that the iron-sulfur clusters have a further role in affecting the DNA-binding properties of WhiB proteins (den Hengst and Buttner, 2008).…”

Section: Detection Of the Repertoire Of Transcription Regulators In Cmentioning

confidence: 99%

The transcriptional regulatory repertoire of Corynebacterium glutamicum: Reconstruction of the network controlling pathways involved in lysine and glutamate production

Brinkrolf

Schröder

Pühler

et al. 2010

Journal of Biotechnology

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“…From previous reports, in the absence of a [4Fe-4S] cluster, the conserved cysteines in all seven of the Mtb Wbl proteins form two intramolecular disulfide bonds: one between the CXXC motif and the other between the other two conserved cysteines [29-31]. Additionally, the Wbl proteins were characterized as protein disulfide reductases whereby the reduction of an intermolecular bond between α- and β-chains of insulin was dependent upon the CXXC motif [23, 29-31]. Notably, insulin reduction was not observed for WhiB2 [23].…”

Section: Whib-like (Wbl) Family Of Proteinsmentioning

confidence: 89%

Insights into redox sensing metalloproteins in Mycobacterium tuberculosis

Chim¹,

Johnson²,

Goulding³

2014

Journal of Inorganic Biochemistry

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Mycobacterium tuberculosis, the pathogen that causes tuberculosis, has evolved sophisticated mechanisms for evading assault by the human host. This review focuses on M. tuberculosis regulatory metalloproteins that are sensitive to exogenous stresses attributed to changes in the levels of gaseous molecules (i.e., molecular oxygen, carbon monoxide and nitric oxide) to elicit an intracellular response. In particular, we highlight recent developments on the subfamily of Whi proteins, redox sensing WhiB-like proteins that contain iron-sulfur clusters, sigma factors and their cognate anti-sigma factors of which some are zinc-regulated, and the dormany survival regulon DosS/DosT-DosR heme sensory system. Mounting experimental evidence suggests that these systems contribute to a highly complex and interrelated regulatory network that controls M. tuberculosis biology. This review concludes with a discussion of strategies M. tuberculosis has developed to maintain redox homeostasis, including mechanisms to regulate endogenous nitric oxide and carbon monoxide levels.

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Characterization of Mycobacterium tuberculosis WhiB1/Rv3219 as a protein disulfide reductase

Cited by 32 publications

References 43 publications

Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis

Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis

The transcriptional regulatory repertoire of Corynebacterium glutamicum: Reconstruction of the network controlling pathways involved in lysine and glutamate production

Insights into redox sensing metalloproteins in Mycobacterium tuberculosis

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