Role of Adenosine Nucleotides in the Regulation of a Stress-response Transcription Factor inBacillus subtilis

Alper, Scott; Dufour, Alain; Garsin, Danielle A.; Duncan, Leonard; Losick, Richard

doi:10.1006/jmbi.1996.0390

Cited by 125 publications

(172 citation statements)

References 27 publications

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“…The two best characterized examples of anti-sigma factors belonging to the GHKL superfamily of ATPases, B. subtilis SpoIIAB and RsbW, are protein kinases that use ATP to phosphorylate and inactivate an antagonist protein (an anti-antisigma factor) (50,51). Because RsmA is a member of the same superfamily, and contains a HATPase_c domain that is characteristic of anti-sigma factors regulating group 3 sigma factors, the interaction of RsmA with nucleotides was investigated.…”

Section: Discussionmentioning

confidence: 99%

RsmA Is an Anti-sigma Factor That Modulates Its Activity through a [2Fe-2S] Cluster Cofactor

Gaskell

Crack²,

Kelemen

et al. 2007

Journal of Biological Chemistry

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The rsmA gene of Streptomyces coelicolor lies directly upstream of the gene encoding the group 3 sigma factor M . The RsmA protein is a putative member of the HATPase_c family of anti-sigma factors but is unusual in that it contains seven cysteine residues. Bacterial two-hybrid studies demonstrate that it interacts specifically with M , and in vitro studies of the purified proteins by native PAGE and transcription assays confirmed that they form a complex. Characterization of RsmA revealed that it binds ATP and that, as isolated, it contains significant quantities of iron and inorganic sulfide, in equal proportion, with spectroscopic properties characteristic of a [2Fe-2S] cluster-containing protein. Importantly, the interaction between RsmA and M is dependent on the presence of the iron-sulfur cluster. We propose a model in which RsmA regulates the activity of M . Loss of the cluster, in response to an as yet unidentified signal, activates M by abolishing its interaction with the anti-sigma factor. This represents a major extension of the functional diversity of iron-sulfur cluster proteins.Iron-sulfur proteins constitute a ubiquitous and hugely functionally diverse family of proteins that contain clusters of iron atoms bridged by acid-labile sulfides. Protein cysteine residue side chains normally complete the tetrahedral coordination of each iron. The capacity to delocalize electrons over both iron and sulfur ions makes iron-sulfur clusters ideally suited to roles in electron transfer pathways such as the respiratory and photosynthetic electron transfer chains and in nitrogen fixation. They are also involved in substrate binding and activation (e.g. in dehydratases such as aconitase and the radical S-adenosylmethionine family of enzymes), sulfur donation (e.g. biotin synthase), and the regulation of enzyme activity (e.g. phosphoribosylpyrophosphate amidotransferase (see Ref. 1 and references therein).In addition to these roles, there are also several well characterized examples of iron-sulfur clusters involved in regulation of gene expression in bacteria. SoxR, which contains a redoxactive [2Fe-2S] cluster (2), responds to oxidative stress and activates SoxS, another transcription factor that, in turn, activates the transcription of the target genes (3, 4). FNR is a CRP-like transcription regulator that controls the expression of genes involved in the adaptation to anoxia (5). The sensory domain (N terminus) binds a [4Fe-4S] cluster that degrades in the presence of O 2 to a [2Fe-2S] cluster via a two-step mechanism involving a [3Fe-4S] cluster intermediate (6), with a concomitant loss of DNA-binding activity (7,8). IscR, a transcription regulator involved in iron-cluster synthesis, requires the presence of a [2Fe-2S] cluster for its activity (9).Transcriptional regulation also occurs through the composition of RNA polymerase holoenzyme (10). In addition to the principle sigma factor, essential for housekeeping functions, many bacteria contain several alternative sigma factors that are required for cellular res...

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Section: Discussionmentioning

confidence: 99%

RsmA Is an Anti-sigma Factor That Modulates Its Activity through a [2Fe-2S] Cluster Cofactor

Gaskell

Crack²,

Kelemen

et al. 2007

Journal of Biological Chemistry

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“…RsbW is both a binding protein and an RsbV-specific kinase. In unstressed B. subtilis, RsbW-dependent phosphorylation of RsbV inactivates RsbV as a potential s B release factor (Alper et al, 1996;Dufour & Haldenwang, 1994). The dephosphorylation and reactivation of RsbV-P are effected by two stress-activated phosphatases, RsbP and RsbU.…”

Section: Introductionmentioning

confidence: 99%

Associations between Bacillus subtilis B regulators in cell extracts

Kuo¹

2004

Microbiology

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The general stress regulon of Bacillus subtilis is induced by the activation of the s B transcription factor. Activation of s B occurs as a consequence of the dephosphorylation of its positive regulator RsbV by one of two phosphatases that respond to either physical or nutritional stress. The physical stress phosphatase (RsbU) requires a second protein (RsbT) for activity. Stress is thought to initiate a process that triggers the release of RsbT from a large inhibitory complex composed of multiple copies of two protein species, RsbR (and/or its paralogues) and RsbS. The stress-derived signal driving RsbT release is unknown, but it fails to develop in B. subtilis lacking either ribosome protein L11 or the ribosome-associated protein Obg. RsbR, RsbS, RsbT, Obg and ribosomes elute in common high-molecular-mass fractions during gel-filtration chromatography of crude B. subtilis extracts. This paper reports the investigation of the basis of this coelution by the examining of associations between these proteins in extracts prepared from wild-type and mutant B. subtilis, and Escherichia coli engineered to express RsbR, RsbS and RsbT. Large RsbR/RsbS complexes, distinct from ribosomes, were detected in extracts of both B. subtilis and E. coli. In E. coli, high-molecular-mass forms of RsbS were less abundant when RsbR was absent, but in B. subtilis, only when both RsbR and its principal paralogues were missing from the extract was this form less abundant. This finding is consistent with the notion that the RsbR paralogues, present in B. subtilis but not E. coli, can substitute for RsbR in such complexes. RsbT was not bound to RsbR/RsbS in any extract that was examined, including one prepared from a B. subtilis strain with an RsbS variant (RsbS59SA) that is believed to continuously associate with RsbT. The high-molecular-mass forms of RsbT were found to be Triton-sensitive and independent of any other B. subtilis protein for their formation. These probably represent RsbT aggregates. The data suggest that the contribution of ribosomes/Obg to s B activation does not involve formation of a stable association between these proteins and the Rsb complex. In addition, the binding of RsbT to RsbS/RsbR appears to be more labile than the binding between the previously analysed Rsb proteins which form inhibitory complexes. This, and the apparent proclivity of RsbT to aggregate, suggests an inherent instability in RsbT which may play a role in its regulation.

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“…The action of RsbW is countered by the RsbV antagonist protein. Whether RsbW forms a complex with B or with its RsbV antagonist is determined by the phosphorylation state of RsbV, which in turn depends upon the opposing activities of the RsbW serine kinase and the RsbU serine phosphatase (Dufour and Haldenwang, 1994;Alper et al, 1996;Yang et al, 1996). Alper et al (1994) have proposed that the activity of the RsbW kinase reflects the energy level of the cell.…”

Section: Introductionmentioning

confidence: 99%

Modulator protein RsbR regulates environmental signalling in the general stress pathway of Bacillus subtilis

Akbar

Kang

Gaidenko

et al. 1997

Molecular Microbiology

131

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Role of Adenosine Nucleotides in the Regulation of a Stress-response Transcription Factor inBacillus subtilis

Cited by 125 publications

References 27 publications

RsmA Is an Anti-sigma Factor That Modulates Its Activity through a [2Fe-2S] Cluster Cofactor

RsmA Is an Anti-sigma Factor That Modulates Its Activity through a [2Fe-2S] Cluster Cofactor

Associations between Bacillus subtilis B regulators in cell extracts

Modulator protein RsbR regulates environmental signalling in the general stress pathway of Bacillus subtilis

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