Sigma factor mimicry involved in regulation of general stress response

Francez‐Charlot, Anne; Frunzke, Julia; Reichen, Christian; Ebneter, Judith Zingg; Gourion, Benjamin; Vorholt, Julia A.

doi:10.1073/pnas.0810291106

Cited by 123 publications

(207 citation statements)

References 41 publications

(54 reference statements)

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“…PhyR is a member of the response regulator family and is unique in that its output domain shows homology to ECF sigma factors (14,15). While the PhyR receiver domain (PhyR REC ) has a classic receiver fold with the conserved phosphorylation site and catalytical motifs, the sigma factor-like output domain (PhyR SL ) essentially retains an ECF sigma factor fold but lacks the σ 2.4 region and is degenerate in the σ 4.2 region, which are normally involved in promoter binding in bona fide ECF sigma factors (12,16). According to the proposed model (12), under unstressed conditions, the sigma factor σ EcfG is sequestered by its anti-sigma factor, NepR, and the anti-sigma factor antagonist, PhyR, remains in an unphosphorylated inactive state.…”

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confidence: 99%

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Structural basis for sigma factor mimicry in the general stress response of Alphaproteobacteria

Campagne

Damberger

Kaczmarczyk³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Reprogramming gene expression is an essential component of adaptation to changing environmental conditions. In bacteria, a widespread mechanism involves alternative sigma factors that redirect transcription toward specific regulons. The activity of sigma factors is often regulated through sequestration by cognate anti-sigma factors; however, for most systems, it is not known how the activity of the anti-sigma factor is controlled to release the sigma factor. Recently, the general stress response sigma factor in Alphaproteobacteria, σ EcfG , was identified. σ EcfG is inactivated by the anti-sigma factor NepR, which is itself regulated by the response regulator PhyR. This key regulator sequesters NepR upon phosphorylation of its PhyR receiver domain via its σ EcfG sigma factor-like output domain (PhyR SL ). To understand the molecular basis of the PhyR-mediated partner-switching mechanism, we solved the structure of the PhyR SL –NepR complex using NMR. The complex reveals an unprecedented anti-sigma factor binding mode: upon PhyR SL binding, NepR forms two helices that extend over the surface of the PhyR SL subdomains. Homology modeling and comparative analysis of NepR, PhyR SL , and σ EcfG mutants indicate that NepR contacts both proteins with the same determinants, showing sigma factor mimicry at the atomic level. A lower density of hydrophobic interactions, together with the absence of specific polar contacts in the σ EcfG –NepR complex model, is consistent with the higher affinity of NepR for PhyR compared with σ EcfG . Finally, by reconstituting the partner switch in vitro, we demonstrate that the difference in affinity of NepR for its partners is sufficient for the switch to occur.

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“…We recently discovered an original anti-sigma factor antagonist, PhyR, involved in a partner-switching mechanism governing the general stress response in Alphaproteobacteria (12)(13)(14). PhyR is a member of the response regulator family and is unique in that its output domain shows homology to ECF sigma factors (14,15).…”

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confidence: 99%

Structural basis for sigma factor mimicry in the general stress response of Alphaproteobacteria

Campagne

Damberger

Kaczmarczyk³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…In Alphaproteobacteria, the GSR is controlled by an alternative extracytoplasmic function (ECF) sigma factor, usually called σ EcfG (1) or ECF15 sigma factor (2), the activity of which is regulated by a conserved partner-switching mechanism (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In unstressed conditions, σ EcfG is sequestered by its anti-sigma factor NepR.…”

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“…Upon stress, the anti-antisigma factor PhyR becomes activated and binds NepR, thereby releasing σ EcfG and allowing it to bind RNA polymerase and redirect transcription toward stress genes. Because PhyR uses a degenerate N-terminal sigma factor-like output domain to compete with σ EcfG for NepR binding, this partner switch was coined "sigma factor mimicry" (1). The importance of the alphaproteobacterial GSR in natural environments is underlined by several studies demonstrating its requirement for survival and competitiveness in the phyllosphere in Sphingomonas melonis (10) and Methylobacterium extorquens (8), the establishment of symbiotic interactions in Bradyrhizobium japonicum (9), and host-pathogen interactions in Brucella (6,11) and Bartonella (3) species.…”

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confidence: 99%

Complex two-component signaling regulates the general stress response in Alphaproteobacteria

Kaczmarczyk¹,

Hochstrasser²,

Vorholt³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Bacteria possess many regulatory systems to monitor their environment and adapt their physiology accordingly. Whereas most systems sense one specific signal, the general stress response (GSR) is activated by many signals and protects cells against a wide range of adverse conditions. In Alphaproteobacteria, the GSR is controlled by the response regulator PhyR, but little is known about the upstream pathways. Here, we establish the GSR as a complex regulatory network composed of a particular family of partially redundant sensor kinases and of additional response regulators that modulate PhyR activity in Sphingomonas melonis . Given the broad conservation of this kinase family, it is possible that it plays a general role in the GSR in Alphaproteobacteria.

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“…Under activating environmental conditions, anti-s factor activity is lost and the s factor is released into the cytoplasm. Inhibition of anti-s factor activity can occur in one of several ways: a conformational change in the structure of the anti-s factor, regulated intramembrane proteolysis (RIP) of the anti-s factor, or phosphorylation and partner switching by an anti-anti-s factor (Ellermeier & Losick, 2006;Francez-Charlot et al, 2009;Heinrich & Wiegert, 2009;Kang et al, 1999;Paget et al, 2001). …”

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confidence: 99%

The atypical two-subunit σ factor from Bacillus subtilis is regulated by an integral membrane protein and acid stress

2016

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The atypical two-subunit s factor from Bacillus subtilis is regulated by an integral membrane protein and acid stress Extracytoplasmic function (ECF) s factors constitute a major component of the physicochemical sensory apparatus in bacteria. Most ECF s factors are co-expressed with a negative regulator called an anti-s factor that binds to its cognate s factor and sequesters it from productive association with core RNA polymerase (RNAP). Anti-s factors constitute an important element of signal transduction pathways that mediate an appropriate transcriptional response to changing environmental conditions. The Bacillus subtilis genome encodes seven canonical ECF s factors and six of these are co-expressed with experimentally verified anti-s factors. B. subtilis also expresses an ECF-like atypical two-subunit s factor composed of subunits SigO and RsoA that becomes active after exposure to certain cell-wall-acting antibiotics and to growth under acidic conditions. This work describes the identification and preliminary characterization of a protein (RsiO, formerly YvrL) that constitutes the anti-s factor cognate to SigO-RsoA. Synthesis of RsiO represses SigO-RsoA-dependent transcription initiation by binding the N-terminus of SigO under neutral (pH 7) conditions. Reconstitution of the SigO-RsoA-RsiO regulatory system into a heterologous host reveals that the imposition of acid stress (pH 5.4) abolishes the ability of RsiO to repress SigO-RsoA-dependent transcription and this correlates with loss of RsiO binding affinity for SigO. A current model for RsiO function indicates that RsiO responds, either directly or indirectly, to increased extracytoplasmic hydrogen ion concentration and becomes inactivated. This results in the release of SigO into the cytoplasm, where it productively associates with RsoA and core RNAP to initiate transcription from target promoters in the cell.

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Sigma factor mimicry involved in regulation of general stress response

Cited by 123 publications

References 41 publications

Structural basis for sigma factor mimicry in the general stress response of Alphaproteobacteria

Structural basis for sigma factor mimicry in the general stress response of Alphaproteobacteria

Complex two-component signaling regulates the general stress response in Alphaproteobacteria

The atypical two-subunit σ factor from Bacillus subtilis is regulated by an integral membrane protein and acid stress

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