Crystal Structure of the Response Regulator 02 Receiver Domain, the Essential YycF Two-Component System of<i>Streptococcus pneumoniae</i>in both Complexed and Native States

Bent, Colin J.; Isaacs, Neil W.; Mitchell, Tim; Riboldi-Tunnicliffe, A.

doi:10.1128/jb.186.9.2872-2879.2004

Cited by 46 publications

(59 citation statements)

References 61 publications

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“…The serine residue (Ser100) has two conformations, one interacting with the phosphoryl oxygen and the other pointing to the solvent. The coupled movements of these two residues have been observed in the BeF 3 Ϫ complex of CheY also (14). The solution structure of NtrC-P (13, 24) displays a different mode of reorientation; however, the available crystallographic data on phosphorylated response regulators or beryllofluoride complexes of response regulators are generally consistent with the pattern described above.…”

Section: Structural Studies Of Spo0fsupporting

confidence: 54%

Conformational Changes of Spo0F along the Phosphotransfer Pathway

Varughese

2005

J Bacteriol

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Spo0F is a secondary messenger in the sporulation phosphorelay, and its structure has been characterized crystallographically in the apo-state, in the metal-bound state, and in an interacting state with a phosphotransferase. Additionally, the solution structure of the molecule has been characterized by nuclear magnetic resonance techniques in the unliganded state and in complex with beryllofluoride. Spo0F is a single-domain protein with a well-defined three-dimensional structure, but it is capable of adapting to specific conformations for catching and releasing the phosphoryl moiety. This commentary deals with the conformational fluctuations of the molecule as it moves from an apo-state to a metal-coordinated state, to a phosphorylated state, and then to a phosphoryl-transferring state.Spo0F is a component of the sporulation phosphorelay of Bacillus subtilis (10) which acts as a gateway for all sporulation signals processed by various histidine kinases (Fig. 1). The initiation of sporulation is controlled by a single parameter, the degree of phosphorylation of the transcription factor Spo0A. It is Spo0F that takes the phosphoryl moiety from the sensor kinases and passes it on to Spo0A through the phosphotransferase Spo0B. Hence, the activity of Spo0F involves interactions with the sensor kinases and Spo0B in receiving and donating the phosphoryl group. Therefore, to describe the conformational pathway of Spo0F, it is necessary to consider four distinct conformational states for Spo0F: (i) isolated unphosphorylated state, (ii) unphosphorylated Spo0F interacting with KinA, (iii) phosphorylated Spo0F, and (iv) phosphorylated Spo0F interacting with Spo0B. Although the documented structural data are inadequate to fully describe all these distinct states, the available data are reviewed here to gain the best understanding of the conformational states of Spo0F. STRUCTURAL STUDIES OF Spo0FUnphosphorylated state. The structure of Spo0F has been studied by both crystallographic and nuclear magnetic resonance (NMR) techniques. This section focuses on the crystallographic results, and NMR studies are discussed in a different section. Structural analysis has been carried out on the metalfree form (17) and on the metal-bound forms (18,19). Spo0F, like all other response regulators, has an ␣/␤ fold with a central ␤-sheet and five helices surrounding it (Fig. 2). The active site is located on the top of the ␤-strands and comprises an acid pocket with three conserved aspartates: Asp10, Asp11, and Asp54. The site of phosphorylation, Asp54, is located at the bottom of a shallow pocket. All phosphoryl transfer reactions make use of cations, and in the two component/phosphorelay systems, it is the response regulators that bind the cations and present them for catalysis. The crystal structures of the metalfree and metal-bound forms are very similar, and the changes are confined mainly to the metal binding site. The most significant difference between the two states of Spo0F is that, in the metal-free structure, the metal cavity is no...

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Section: Structural Studies Of Spo0fsupporting

confidence: 54%

Conformational Changes of Spo0F along the Phosphotransfer Pathway

Varughese

2005

J Bacteriol

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“…The structure of ArcA N is strikingly similar to that of the regulatory domain of MicA (RR02), an OmpR/PhoB subfamily RR from Streptococcus pneumoniae, recently reported by Bent et al 49 In the unphosphorylated apo-structure, they found an extensive dimer interface created by a two-fold crystallographic axis and suggested that it represented of the active dimer conformation. The ArcA N and MicA N dimers superimpose very well with an rmsd of 1.265 Å for all Cα atoms ( Fig.…”

Section: Dimer Interfacementioning

confidence: 77%

“…A multiple sequence alignment of the regulatory domains of all members of this subfamily from E. coli, 20 in addition to subfamily members from other organisms for which structures of the regulatory domain are available, 33,34,49,50 revealed that the residues involved in key dimer interface interactions are highly conserved within this subfamily (Fig. 5).…”

Section: Dimer Interfacementioning

confidence: 99%

Structural Analysis and Solution Studies of the Activated Regulatory Domain of the Response Regulator ArcA: A Symmetric Dimer Mediated by the α4-β5-α5 Face

Toro-Roman

Mack²,

Stock

2005

Journal of Molecular Biology

119

137

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SUMMARYEscherichia coli react to changes from aerobic to anaerobic conditions of growth using the ArcAArcB two-component signal transduction system. This system, in conjunction with other proteins, regulates the respiratory metabolic pathways in the organism. ArcA is a member of the OmpR/ PhoB subfamily of response regulator transcription factors that are known to regulate transcription by binding in tandem to target DNA direct repeats. It is still unclear in this subfamily how activation by phosphorylation of the regulatory domain of response regulators stimulates DNA binding by the effector domain and how dimerization and domain orientation, as well as intra-and intermolecular interactions, affect this process. In order to address these questions we have solved the crystal structure of the regulatory domain of ArcA in the presence and absence of the phosphoryl analog, BeF 3 − . In the crystal structures, the regulatory domain of ArcA forms a symmetric dimer mediated by the α4-β5-α5 face of the protein and involving a number of residues that are highly conserved in the OmpR/PhoB subfamily. It is hypothesized that members of this subfamily use a common mechanism of regulation by dimerization. Additional biophysical studies were employed to probe the oligomerization state of ArcA, as well as its individual domains, in solution. The solution studies show the propensity of the individual domains to associate into oligomers larger than the dimer observed for the intact protein, and suggest that the C-terminal DNA-binding domain also plays a role in oligomerization.

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“…Several crystal structures of receiver domains of response regulators have been solved (43)(44)(45)(46), but little structural information is available regarding how they interact with each other in multiprotein complexes. As well, knowledge of the structure of the receiver domain in complex with the connector protein is limited.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis of a Physical Blockage Mechanism for the Interaction of Response Regulator PmrA with Connector Protein PmrD from Klebsiella pneumoniae

Luo

Lou

Rajasekaran

et al. 2013

Journal of Biological Chemistry

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Background: PmrD binds to phospho-PmrA and sustains its phosphorylation state. Results: Phospho-PmrA interacts with PmrD via several specific intermolecular interactions. Conclusion: A steric inhibition mechanism was proposed for protecting phospho-PmrA against dephosphorylation. Significance: This work provides novel data revealing how a connector protein protects an activated response regulator.

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Crystal Structure of the Response Regulator 02 Receiver Domain, the Essential YycF Two-Component System ofStreptococcus pneumoniaein both Complexed and Native States

Cited by 46 publications

References 61 publications

Conformational Changes of Spo0F along the Phosphotransfer Pathway

Conformational Changes of Spo0F along the Phosphotransfer Pathway

Structural Analysis and Solution Studies of the Activated Regulatory Domain of the Response Regulator ArcA: A Symmetric Dimer Mediated by the α4-β5-α5 Face

Structural Basis of a Physical Blockage Mechanism for the Interaction of Response Regulator PmrA with Connector Protein PmrD from Klebsiella pneumoniae

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