How the “Melting” and “Freezing” of Protein Molecules May Be Used in Cell Signaling

Bray, Dennis; Williams, Dudley H.

doi:10.1021/cb800024g

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…One possibility is that the binding of salicylate to Rob does not yield any appreciable enthalpic change. Rather, binding could yield an entropic change, possibly by disordering the protein (7,59). Such a binding mechanism would not be detected using isothermal calorimetry.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Cross Talk within themar-sox-robRegulon in Escherichia coli Is Limited to therobandmarRABOperons

Chubiz¹,

Glekas²,

Rao³

2012

J. Bacteriol.

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ABSTRACTBacteria possess multiple mechanisms to survive exposure to various chemical stresses and antimicrobial compounds. In the enteric bacteriumEscherichia coli, three homologous transcription factors—MarA, SoxS, and Rob—play a central role in coordinating this response. Three separate systems are known to regulate the expression and activities of MarA, SoxS, and Rob. However, a number of studies have shown that the three do not function in isolation but rather are coregulated through transcriptional cross talk. In this work, we systematically investigated the extent of transcriptional cross talk in themar-sox-robregulon. While the three transcription factors were found to have the potential to regulate each other's expression when ectopically expressed, the only significant interactions observed under physiological conditions were betweenmarandrobsystems. MarA, SoxS, and Rob all activate themarRABpromoter, more so when they are induced by their respective inducers: salicylate, paraquat, and decanoate. None of the three proteins affects thesoxSpromoter, though unexpectedly, it was mildly repressed by decanoate by an unknown mechanism. SoxS is the only one of the three proteins to repress therobpromoter. Surprisingly, salicylate somewhat activates transcription ofrob, while decanoate represses it a bit. Rob, in turn, activates not only its downstream promoters in response to salicylate but also themarRABpromoter. These results demonstrate that themarandrobsystems function together in response to salicylate.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Cross Talk within themar-sox-robRegulon in Escherichia coli Is Limited to therobandmarRABOperons

Chubiz¹,

Glekas²,

Rao³

2012

J. Bacteriol.

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“…A growing body of evidence links the signaling properties of MCP molecules to their structural stabilities or dynamic motions. Recep-tor molecules in clustered arrays, for example, seem to freeze or melt in response to stimulus inputs (12), which confers high cooperativity and signal amplification (32). These dynamic effects are best understood for the adaptation region of the MH bundle, where methylation and demethylation changes affect the stability of helix-helix interactions (46,60).…”

Section: Dynamic Influences On Output Signalsmentioning

confidence: 99%

Signaling Mechanisms of HAMP Domains in Chemoreceptors and Sensor Kinases

Parkinson

2010

Annu. Rev. Microbiol.

174

245

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HAMP domains mediate input-output signaling in histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis proteins, and some phosphatases. HAMP subunits have two 16-residue amphiphilic helices (AS1, AS2) joined by a 14- to 15-residue connector segment. Two alternative HAMP structures in these homodimeric signaling proteins have been described: HAMP(A), a tightly packed, parallel, four-helix bundle; and HAMP(B), a more loosely packed bundle with an altered AS2/AS2' packing arrangement. Stimulus-induced conformational changes probably modulate HAMP signaling by shifting the relative stabilities of these opposing structural states. Changes in AS2/AS2' packing, in turn, modulate output signals by altering structural interactions between output helices through heptad repeat stutters that produce packing phase clashes. Output helices that are too tightly or too loosely packed most likely produce kinase-off output states, whereas kinase-on states require an intermediate range of HAMP stabilities and dynamic behaviors. A three-state, dynamic bundle signaling model best accounts for the signaling properties of chemoreceptor mutants and may apply to other transducers as well.

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“…This is especially interesting because our previous analyses have shown that chemoreceptor ''zippers'' can coexist with chemoreceptor/CheA/CheW complexes in cells where Tsr is selectively overproduced (30), suggesting that axial receptorreceptor interactions in the ''zipper'' region may mimic receptor-CheA/CheW interactions in the wild-type signaling array. Furthermore, the ''zipper''-like arrangement may inhibit larger-scale arrangements of the receptors that may include intertwined trimers of dimers that have been proposed to be involved in kinase down-regulation (22,31). Application of the methodologies developed here to chemoreceptor arrays in wild-type E. coli cells and those of other Gram-negative bacteria (32) should help further elucidate the conformational changes involved in chemotaxis signaling.…”

Section: Effects Of Ligand Binding and Methylation On Chemoreceptor Cmentioning

confidence: 99%

Role of HAMP domains in chemotaxis signaling by bacterial chemoreceptors

Khursigara

Zhang

et al. 2008

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

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Bacterial chemoreceptors undergo conformational changes in response to variations in the concentration of extracellular ligands. These changes in chemoreceptor structure initiate a series of signaling events that ultimately result in regulation of rotation of the flagellar motor. Here we have used cryo-electron tomography combined with 3D averaging to determine the in situ structure of chemoreceptor assemblies in Escherichia coli cells that have been engineered to overproduce the serine chemoreceptor Tsr. We demonstrate that chemoreceptors are organized as trimers of receptor dimers and display two distinct conformations that differ principally in arrangement of the HAMP domains within each trimer. Ligand binding and methylation alter the distribution of chemoreceptors between the two conformations, with serine binding favoring the ''expanded'' conformation and chemoreceptor methylation favoring the ''compact'' conformation. The distinct positions of chemoreceptor HAMP domains within the context of a trimeric unit are thus likely to represent important aspects of chemoreceptor structural changes relevant to chemotaxis signaling. Based on these results, we propose that the compact and expanded conformations represent the ''kinase-on'' and ''kinaseoff'' states of chemoreceptor trimers, respectively.cryo-electron tomography ͉ molecular architecture ͉ signal transduction M otile bacteria such as Escherichia coli respond to changes in their chemical environment by recognizing variations in the ligand occupancy of a series of transmembrane chemoreceptors (also known as methyl-accepting chemotaxis proteins, or MCPs). Ligand binding to chemoreceptors initiates a signaling cascade that modulates the activity of the histidine kinase CheA, which ultimately regulates the rotation of the flagellar motor through a diffusible intracellular signal (1, 2). Chemoreceptors exist as homodimers and have been shown to function as trimers of chemoreceptor dimers both in vitro (3) and in vivo (4-6).Chemoreceptor homodimers can be divided into three functional modules, each of which plays a critical role in receptormediated signaling (7). The transmembrane-sensing module is composed of both the sensing domain, which resides in the periplasm and contains the ligand binding site (8), and the transmembrane portion of the chemoreceptor. It has been deduced that ligand binding to the periplasmic domain results in a piston-like sliding motion of one of the four transmembrane helices (7, 9). The highly conserved cytoplasmic region of chemoreceptors can be divided into two functional modules: the signal conversion module, which contains a HAMP (histidine kinase, adenylyl cyclases, methyl-binding proteins, and phosphatases) domain, and a kinase control module, which contains an adaptation region and a protein interaction region (7, 9). The HAMP domain is the proposed site of signal conversion between the transmembrane-sensing and kinase control modules (7). The recent solution structure of an archaeal HAMP domain demonstrates that it adopts a ho...

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How the “Melting” and “Freezing” of Protein Molecules May Be Used in Cell Signaling

Cited by 6 publications

References 19 publications

Transcriptional Cross Talk within themar-sox-robRegulon in Escherichia coli Is Limited to therobandmarRABOperons

Transcriptional Cross Talk within themar-sox-robRegulon in Escherichia coli Is Limited to therobandmarRABOperons

Signaling Mechanisms of HAMP Domains in Chemoreceptors and Sensor Kinases

Role of HAMP domains in chemotaxis signaling by bacterial chemoreceptors

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