Crystal Structure of the Full-Length Sorbitol Operon Regulator SorC from Klebsiella pneumoniae: Structural Evidence for a Novel Transcriptional Regulation Mechanism

Sanctis, Daniele de; McVey, Colin E.; Enguita, Francisco J.; Carrondo, Maria Arménia

doi:10.1016/j.jmb.2009.02.017

Cited by 14 publications

(24 citation statements)

References 34 publications

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“…Complementation of this mutation with a sorC + allele restored gene expression of the sorbitol operon. More recently the crystal structure of SorC has been solved, and based on the structural model, a model of the positive and negative transcriptional regulation has been proposed (de Sanctis et al, 2009). The SorC data are analogous to what we observed with eryD (Table 4).…”

Section: Discussionsupporting

confidence: 76%

A locus necessary for the transport and catabolism of erythritol in Sinorhizobium meliloti

et al. 2010

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In this work we have genetically defined an erythritol utilization locus in Sinorhizobium meliloti. A cosmid containing the locus was isolated by complementation of a transposon mutant and was subsequently mutagenized using Tn5 : : B20. The locus was found to consist of five transcriptional units, each of which was necessary for the utilization of erythritol. Genetic complementation experiments using genes putatively annotated as erythritol catabolic genes clearly showed that, of the 17 genes at this locus, six genes are not necessary for the utilization of erythritol as a sole carbon source. The remaining genes encode EryA, EryB, EryC and TpiB as well as an uncharacterized ABC-type transporter. Transport experiments using labelled erythritol showed that components of the ABC transporter are necessary for the uptake of erythritol. The locus also contains two regulators: EryD, a SorC class regulator, and SMc01615, a DeoR class regulator. Quantitative RT-PCR experiments showed that each of these regulators negatively regulates its own transcription. In addition, induction of the erythritol locus was dependent upon EryD and a product of erythritol catabolism. Further characterization of polar mutations revealed that in addition to erythritol, the locus contains determinants for adonitol and L-arabitol utilization. The context of the mutations suggests that the locus is important for both the transport and catabolism of adonitol and L-arabitol.

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Section: Discussionsupporting

confidence: 76%

A locus necessary for the transport and catabolism of erythritol in Sinorhizobium meliloti

et al. 2010

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“…In contrast, the assembly of LsrR tetramer could be regarded as the dimer of two LsrR dimers, which has been observed in other transcriptional regulators. For example, the tetrameric assembly of the full-length sorbitol operon regulator SorC from K. pneumoniae, which can be viewed as the dimer of two dimers, is similar to the LsrR tetramer (31).…”

Section: Resultsmentioning

confidence: 99%

“…The ligand-binding site in CggR complexed with regulatory molecules is located in this groove (33). Although the structure of the SorC and L-sorbose complex was not obtained, a cavity search and in silico docking predicted a groove in the same position to bind ligand (31). The groove in LsrR was composed of the helices ␣5, ␣6, ␤7, and loops connecting ␤3-␣6, ␤7-␤8, ␤6-␣11, and ␤9-␣14 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural Basis for Phosphorylated Autoinducer-2 Modulation of the Oligomerization State of the Global Transcription Regulator LsrR from Escherichia coli

Wu¹,

Tao²,

Liu

et al. 2013

Journal of Biological Chemistry

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Background:The Escherichia coli global transcription regulator LsrR regulates the expression of many genes in response to autoinducer-2. Results: We determined the crystal structure of LsrR and demonstrated that phosphorylated autoinducer-2 triggers the disassembly of LsrR tetramers. Conclusion: Our findings reveal a possible mechanism for the change in the oligomerization state of LsrR. Significance: These observations may shed light on a gene transcription mechanism.

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“…Interestingly, there are additional secondary structure elements annotated by β0 and α″1/2, which seems to be important for binding to a target DNA and a ligand, respectively (Figure 1B and C). The overall architecture of LsrR tetramer can be described as dimer of two dimers, very similar to the sorbitol operon regulator, SorC 24 . The crystal structure of LsrR shows the presence of two different inter-molecular interactions; (i) The first one (interface-1) stabilizes the dimer of subunit-A/B or subunit-C/D, and is the same dimeric interface of C-LsrR.…”

Section: Resultsmentioning

confidence: 99%

“…Overall transcriptional regulation of the LsrR protein by the D5P-binding can be inferred from the previous studies on the SorC protein family including the CggR (central glycolytic genes regulator) and DeoR proteins 24 . As described in a recently published paper 23 , the architecture of the lsr operator region is similar to that of the CggR-regulated gapA operon 33 and the two recognition sites of LsrR also do not have identical sequences 33 .…”

Section: Discussionmentioning

confidence: 99%

Crystal Structures of the LsrR Proteins Complexed with Phospho-AI-2 and Two Signal-Interrupting Analogues Reveal Distinct Mechanisms for Ligand Recognition

Grishaev

et al. 2013

J. Am. Chem. Soc.

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Quorum sensing (QS) is a cell-to-cell communication system and responsible for a variety of bacterial phenotypes including virulence and biofilm formation. QS is mediated by small molecules, autoinducers (AIs), including AI-2 that is secreted by both Gram (+/−) microbes. LsrR is a key transcriptional regulator that governs the varied downstream processes by perceiving AI-2 signal, but its activation via autoinducer-binding remains poorly understood. Here, we provide detailed regulatory mechanism of LsrR from the crystal structures in complexes with the native signal (phospho-AI-2, D5P) and two quorum quenching antagonists (ribose-5-phosphate, R5P; phospho-isobutyl-AI-2, D8P). Interestingly, the bound D5P and D8P molecules are not the diketone forms but rather hydrated, and the hydrated moiety forms important H-bonds with the carboxylate of D243. The D5P-binding flipped out F124 of the binding pocket, and resulted in the disruption of the dimeric interface-1 by unfolding the α7 segment. However, the same movement of F124 by the D8P′-binding did not cause the unfolding of the α7 segment. Although the LsrR-binding affinity of R5P (Kd, ~1 mM) is much lower than those of D5P and D8P (~2.0 and ~0.5 μM), the α-anomeric R5P molecule fits into the binding pocket without any structural perturbation, and thus stabilizes the LsrR tetramer. The binding of D5P, not D8P and R5P, disrupted the tetrameric structure and thus is able to activate LsrR. The detailed structural and mechanistic insights from this study could be useful for facilitating design of new anti-virulence and anti-biofilm agents based on LsrR.

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Crystal Structure of the Full-Length Sorbitol Operon Regulator SorC from Klebsiella pneumoniae: Structural Evidence for a Novel Transcriptional Regulation Mechanism

Cited by 14 publications

References 34 publications

A locus necessary for the transport and catabolism of erythritol in Sinorhizobium meliloti

A locus necessary for the transport and catabolism of erythritol in Sinorhizobium meliloti

Structural Basis for Phosphorylated Autoinducer-2 Modulation of the Oligomerization State of the Global Transcription Regulator LsrR from Escherichia coli

Crystal Structures of the LsrR Proteins Complexed with Phospho-AI-2 and Two Signal-Interrupting Analogues Reveal Distinct Mechanisms for Ligand Recognition

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