Crystal Structure of the
            <i>Staphylococcus aureus</i>
            pI258 CadC Cd(II)/Pb(II)/Zn(II)-Responsive Repressor

Ye, Jun; Kandegedara, Ashoka; Martin, Philip D.; Rosen, Barry P.

doi:10.1128/jb.187.12.4214-4221.2005

Cited by 94 publications

(138 citation statements)

References 36 publications

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“…A search of the Protein Data Bank using the DALI server (30) identifies BigR, HylU, and CadC as the closest structural relatives of NolR (Fig. S1 B-D) with Z-scores of 14.4-14.9 and 2.0-2.7 Å rmsd for 95-97 Cα atoms (26,(31)(32)(33). The major differences between these proteins occur in the length and positioning of the N-terminal α-helical region at the dimerization interface ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In the ArsR/SmtB proteins, metal binding triggers conformational changes that result in derepression of gene expression by driving repositioning of the helix-turn-helix DNA interaction motif (26)(27)(28)(29)(31)(32)(33). This movement results in a switch from a "closed" DNA-binding structure to an "open" low-affinity conformation of the homodimer.…”

Section: Discussionmentioning

confidence: 99%

“…S1). Unlike other ArsR/ SmtB transcription factors (26)(27)(28)(29)(31)(32)(33), no global structural Titrations were performed using 22-bp DNA duplexes.…”

Section: Discussionmentioning

confidence: 99%

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Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR

Lee

Krishnan

Jez

2014

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

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The symbiosis between rhizobial microbes and host plants involves the coordinated expression of multiple genes, which leads to nodule formation and nitrogen fixation. As part of the transcriptional machinery for nodulation and symbiosis across a range of Rhizobium, NolR serves as a global regulatory protein. Here, we present the X-ray crystal structures of NolR in the unliganded form and complexed with two different 22-base pair (bp) double-stranded operator sequences (oligos AT and AA). Structural and biochemical analysis of NolR reveals protein-DNA interactions with an asymmetric operator site and defines a mechanism for conformational switching of a key residue (Gln56) to accommodate variation in target DNA sequences from diverse rhizobial genes for nodulation and symbiosis. This conformational switching alters the energetic contributions to DNA binding without changes in affinity for the target sequence. Two possible models for the role of NolR in the regulation of different nodulation and symbiosis genes are proposed. To our knowledge, these studies provide the first structural insight on the regulation of genes involved in the agriculturally and ecologically important symbiosis of microbes and plants that leads to nodule formation and nitrogen fixation.transcription factor | protein structure T he symbiosis between rhizobial bacteria from the Rhizobium, Sinorhizobium, Mesorhizobium, Azorhizobium, and Bradyrhizobium genera and leguminous plants leads to the formation of root nodules (1, 2). These plant organs are specialized for nitrogen fixation and assimilation and are of major ecological and agricultural importance. For example, nitrogen-fixing nodules account for one quarter of total nitrogen fixed globally each year (3). The development of nitrogen-fixing nodules by rhizobia involves a variety of interactions between the plant and microbe; however, at the center of this process are a set of nod (nodulation) genes required for the synthesis of oligosaccharide-nodulation factors, for determining host-plant specificity, and for optimizing the efficiency of symbiosis (4-6). Successful interaction between the rhizobium and host plant requires expression of both positive and negative transcriptional control of genes related to nodulation and symbiosis (7,8

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR

Lee

Krishnan

Jez

2014

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

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“…CadC possesses a unique N-terminal ␣-helix (denoted ␣0 in Fig. 5A) which forms a significant part of the dimer interface in apo-CadC (35). If this ␣0-mediated interprotomer interaction Table 1.…”

Section: Discussionmentioning

confidence: 99%

Solution structure of a paradigm ArsR family zinc sensor in the DNA-bound state

Arunkumar

Campanello

Giedroc

2009

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

180

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Staphylococcus aureusCzrA is a zinc-dependent transcriptional repressor from the ubiquitous ArsR family of metal sensor proteins. Zn(II) binds to a pair of intersubunit C-terminal ␣5-sensing sites, some 15 Å distant from the DNA-binding interface, and allosterically inhibits DNA binding. This regulation is characterized by a large allosteric coupling free energy (⌬Gc) of approximately ؉6 kcal mol ؊1 , the molecular origin of which is poorly understood. Here, we report the solution quaternary structure of homodimeric CzrA bound to a palindromic 28-bp czr operator, a structure that provides an opportunity to compare the two allosteric ''end'' states of an ArsR family sensor. Zn ( M etal ion homeostasis is a complex process that involves maintaining a delicate balance between metal uptake/ efflux and other metal storage systems to meet the needs of the cell (1, 2). This process is tightly regulated at the level of transcription by means of specific metal-dependent transcriptional regulators that respond to changes in metal ion concentrations in the host environment (3). In Staphylococcus aureus, the czr operon encodes a CDF antiporter, CzrB, a homolog of Escherichia coli zinc transporter YiiP that confers resistance to Zn(II) and Co(II) (4, 5), and the metal-regulated repressor, CzrA (6, 7). CzrA binds Zn(II) with picomolar affinity and strong negative homotropic cooperativity (8, 9) and is thought to undergo a conformational change that alleviates transcriptional repression of the resistance gene czrB.CzrA belongs to the ubiquitous ArsR (or ArsR/SmtB) family of metalloregulators found in many bacterial genomes that sense a wide variety of metals including biologically essential metals as well as toxic metal pollutants (10, 11). Members of this family appear to adopt a common winged helix-turn-helix homodimeric fold, but have evolved physically and structurally distinct pairs of allosteric metal-sensing sites (2, 12). These sites are thought to have arisen as a result of convergent evolution due to evolutionary pressures (12), a finding consistent with the ''rule of varied allosteric control'' in which protein families evolve seemingly random allosteric control pathways (13). CzrA and its homolog SmtB in Synechococcus (14) are ␣5 sensors that bind Zn(II) ions in two rotationally symmetric tetrahedral coordination sites formed by pairs of metal ligands derived from the ␣5 helix of each subunit (8). The crystal structure of CzrA and SmtB in the apo and the Zn(II)-bound states have been solved (8). Although the structures of CzrA were found to be very similar in these two states, SmtB revealed measurable differences in quaternary structure in which the apo form adopted a comparatively ''flat'' conformation not well suited to interact with canonical B-form DNA (8,15). The structural and thermodynamic underpinnings of metalloregulation for any member of the ubiquitous ArsR family remains poorly understood due to a lack of detailed insight for the DNA operator-bound state (3).We report here the NMR solution structure of ...

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“…However, even in this well-studied regulator family, the determinants conferring metal specificity are only beginning to be understood. The elegant crystal structure of CadC by Ye et al (26) published in this issue of the Journal of Bacteriology advances our knowledge on two crucial points. First, it reinforces the notion that coordination of a metal and subsequent specific conformational changes or steric hindrance is responsible for metal specificity.…”

mentioning

confidence: 99%

Form and Function in Metal-Dependent Transcriptional Regulation: Dawn of the Enlightenment

Rensing

2005

J Bacteriol

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Metal homeostasis is a complicated process involving uptake, efflux, and sequestration of metals. The processes have to be very carefully regulated at different levels. Metal-dependent transcriptional regulation is the major mechanism of the cellular response to changing metal concentrations. It is therefore crucial to understand how metalloregulators are able to differentiate between metals and how this information is translated into transcriptional control. The ArsR/SmtB family of metalloregulators is present in many bacteria and archaea, and its members respond to a variety of different metals. However, even in this well-studied regulator family, the determinants conferring metal specificity are only beginning to be understood. The elegant crystal structure of CadC by Ye et al. (26) published in this issue of the Journal of Bacteriology advances our knowledge on two crucial points. First, it reinforces the notion that coordination of a metal and subsequent specific conformational changes or steric hindrance is responsible for metal specificity. In other words, nature builds its protein structure around the inherent chemical properties of a metal. Second, the structure of CadC may shed light on the evolutionary history of the ArsR/SmtB family. The members most closely related to a common ancestor, represented by the ArsR family, contain only a type 1 metal binding site, while the more divergent homologue SmtB possesses only a type 2 metal binding site. CadC, with both types of metal-binding sites, might represent an evolutionary intermediate between ArsR and SmtB.Members of the ArsR/SmtB family of metalloregulatory proteins possess a highly conserved DNA recognition helixturn-helix domain and bind as homodimers to their operator/ promoter (O/P) sequences, repressing transcription of the operon. Metal binding to some family members presumably leads to derepression by inducing a conformational change leading to the release of the metalated repressor from the O/P sequence. In the case of CadC, Ye et al. postulate that binding of the metal brings the N terminus of one subunit into position to sterically block the DNA binding site of the other subunit (Fig. 1) It has become clear that simple knowledge of the affinity of a repressor for metal is not enough to predict in vivo functionality. A good example is Escherichia coli NikR.

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Crystal Structure of the Staphylococcus aureus pI258 CadC Cd(II)/Pb(II)/Zn(II)-Responsive Repressor

Cited by 94 publications

References 36 publications

Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR

Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR

Solution structure of a paradigm ArsR family zinc sensor in the DNA-bound state

Form and Function in Metal-Dependent Transcriptional Regulation: Dawn of the Enlightenment

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