Domain swapping in the sporulation response regulator Spo0A

Lewis, Richard J.; Muchová, Katarı́na; Brannigan, J.A.; Barák, Imrich; Leonard, Gordon A.; Wilkinson, Anthony J.

doi:10.1006/jmbi.2000.3598

Cited by 67 publications

(61 citation statements)

References 57 publications

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“…Dimerization is mediated by the receiver domains that associate through molecular twofold symmetry (3). Spo0A also dimerizes upon phosphorylation, and interestingly, unphosphorylated dimers of the full-length protein obtained through ␣5 exchange between two receiver domains activate transcription (32,33). This observation indicates that the dimeric state favors protein binding to the 7-bp DNA consensus sequence of the 0A boxes and seems to be in agreement with the head-to-tail binding of Spo0A to two 0A boxes (5).…”

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confidence: 72%

“…The structural similarities among the effector modules in OmpR, PhoB, and DrrD (24,29,38,45) and among regulatory domains in general (2,7,13,18,19,23,32,37,41,48,49,51,52) are in sharp contrast to the different strategies that are used in the response regulators to regulate protein activity and to respond to the common phosphorylation event. The spatial extent and magnitude of the conformational changes in the ␣4-␤5-␣5 region that essentially sense phosphorylation of the aspartic acid vary in the few regulatory domains that have been characterized in both states (3,10,20,28,31).…”

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confidence: 99%

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The Crystal Structure of the Phosphorylation Domain in PhoP Reveals a Functional Tandem Association Mediated by an Asymmetric Interface

et al. 2003

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PhoP from Bacillus subtilis belongs to the OmpR subfamily of response regulators. It regulates the transcription of several operons and participates in a signal transduction network that controls adaptation of the bacteria to phosphate deficiency. The receiver domains of two members of this subfamily, PhoB from Escherichia coli and DrrD from Thermotoga maritima, have been structurally characterized. These modules have similar overall folds but display remarkable differences in the conformation of the ␤4-␣4 and ␣4 regions. The crystal structure of the receiver domain of PhoP (PhoPN) described in this paper illustrates yet another geometry in this region. Another major issue of the structure determination is the dimeric state of the protein and the novel mode of association between receiver domains. The protein-protein interface is provided by two different surfaces from each protomer, and the tandem unit formed through this asymmetric interface leaves free interaction surfaces. This design is well suited for further association of PhoP dimers to form oligomeric structures. The interprotein interface buries 970 Å 2 from solvent and mostly involves interactions between charged residues. As described in the accompanying paper, mutations of a single residue in one salt bridge shielded from solvent prevented dimerization of the unphosphorylated and phosphorylated response regulator and had drastic functional consequences. The three structurally documented members of the OmpR family (PhoB, DrrD, and PhoP) provide a framework to consider possible relationships between structural features and sequence signatures in critical regions of the receiver domains.

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confidence: 72%

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confidence: 99%

The Crystal Structure of the Phosphorylation Domain in PhoP Reveals a Functional Tandem Association Mediated by an Asymmetric Interface

et al. 2003

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“…It comprises a constellation of five residues that are strongly conserved across the RR family, shown in Fig. 2B [31]. The deduced protein product of Orf22 exhibits similarity to members of the EnvZ family of HK, including the H-box (His-283 being the putative phosphorylation site) and the N and G motifs [32,33] (Fig.…”

Section: Discussionmentioning

confidence: 99%

A Two-component Regulatory System Involved in Clavulanic Acid Production

Jnawali

Liou

et al. 2008

J Antibiot

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A pair of genes encoding the bacterial twocomponent regulatory system, orf22 and orf23, was found next to the clavulanic acid gene cluster of Streptomyces clavuligerus NRRL3585. Orf23 was deleted for the construction of S. clavuligerus/D orf23. Although growth and morphological analyses showed no differences between S. clavuligerus/D orf23 and wild-type, the production of clavulanic acid in S. clavuligerus/D orf23 was found to be decreased. In addition, the co-overexpression of orf22/orf23 in wild-type resulted in an enhanced 1.49-fold production of clavulanic acid, and the complementation of orf22/orf23 in S. clavuligerus/D orf23 restored clavulanic acid production about 80% as normal levels. These results demonstrate that the orf22/orf23 two-component regulatory system participates as a positive regulator of the biosynthesis of clavulanic acid and increased levels of orf22/orf23 can contribute to enhanced production of clavulanic acid in S. clavuligerus.

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“…Structural analyses of the receiver domains of response regulators have revealed a conformational change involving displacement of ␤ strands 4 and 5, as well as ␣ helices 3 and 4, away from the active site (8,13,27,(31)(32)(33). These structural rearrangements in the receiver domain result in changes that affect the activity of output domains, including dimer-multimer formation (5,17,24,34,56), and/or that relieve the inhibitory effect by the receiver domain (3,6,15,16,23,37,66,68).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Activation byBacillus subtilisResD: Tandem Binding to Target Elements and Phosphorylation-Dependent and -Independent Transcriptional Activation

Geng

Nakano

2004

J Bacteriol

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The expression of genes involved in nitrate respiration in Bacillus subtilis is regulated by the ResD-ResE two-component signal transduction system. The membrane-bound ResE sensor kinase perceives a redoxrelated signal(s) and phosphorylates the cognate response regulator ResD, which enables interaction of ResD with ResD-dependent promoters to activate transcription. Hydroxyl radical footprinting analysis revealed that ResD tandemly binds to the ؊41 to ؊83 region of hmp and the ؊46 to ؊92 region of nasD. In vitro runoff transcription experiments showed that ResD is necessary and sufficient to activate transcription of the ResDE regulon. Although phosphorylation of ResD by ResE kinase greatly stimulated transcription, unphosphorylated ResD, as well as ResD with a phosphorylation site (Asp57) mutation, was able to activate transcription at a low level. The D57A mutant was shown to retain the activity in vivo to induce transcription of the ResDE regulon in response to oxygen limitation, suggesting that ResD itself, in addition to its activation through phosphorylation-mediated conformation change, senses oxygen limitation via an unknown mechanism leading to anaerobic gene activation.Bacillus subtilis senses extracellular oxygen limitation and adapts to a new environment by switching to anaerobic metabolism (for reviews see references 50 and 51). When nitrate is available under anaerobic conditions, B. subtilis undergoes nitrate respiration. To successfully switch from aerobic growth to nitrate respiration, the ResD-ResE two-component signal transduction system must be activated, which allows induction of genes that function in nitrate respiration, including fnr (encoding the anaerobic gene regulator Fnr), nasDEF (encoding the nitrite reductase operon), and hmp (encoding the flavohemoglobin) (29,46,52,63). Activation of the signal transduction system commences by sensing by ResE of unidentified signals, followed by autophosphorylation at the conserved histidine residue. The phosphoryl residue is then transferred to the N-terminal aspartate of the cognate response regulator ResD, which leads to activation of the target genes.Most response regulators consist of two domains, a conserved N-terminal receiver (regulatory) domain and a variable C-terminal effector domain (for a review see reference 62). The receiver domains of response regulators are doubly wound ␣/␤ proteins with a central five-strand parallel ␤ sheet surrounded by five ␣ helices, suggesting that there is a common mechanism for phosphorylation and phosphorylation-mediated signal transmission. ResD belongs to an OmpR subfamily whose C-terminal region has a winged helix-turn-helix motif (for reviews see references 26 and 40). Structural analyses of response regulators of this class have been described for each domain (9,28,39,54,61) and for a full-length protein (11,59).These structural studies revealed an overall similarity, as well as characteristic differences, among the members of the same family of response regulators. The most apparent differences are ...

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Domain swapping in the sporulation response regulator Spo0A

Cited by 67 publications

References 57 publications

The Crystal Structure of the Phosphorylation Domain in PhoP Reveals a Functional Tandem Association Mediated by an Asymmetric Interface

The Crystal Structure of the Phosphorylation Domain in PhoP Reveals a Functional Tandem Association Mediated by an Asymmetric Interface

A Two-component Regulatory System Involved in Clavulanic Acid Production

Transcriptional Activation byBacillus subtilisResD: Tandem Binding to Target Elements and Phosphorylation-Dependent and -Independent Transcriptional Activation

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