Artykuły w czasopismach: „Σ/anti–σ factor Interactions”

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Jamithireddy, Anil Kumar, Ashish Runthala i Balasubramanian Gopal. "Evaluation of specificity determinants in Mycobacterium tuberculosis σ/anti-σ factor interactions". Biochemical and Biophysical Research Communications 521, nr 4 (styczeń 2020): 900–906. http://dx.doi.org/10.1016/j.bbrc.2019.10.198.

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Shukla, Jinal, Radhika Gupta, Krishan Gopal Thakur, Rajesh Gokhale i B. Gopal. "Structural basis for the redox sensitivity of theMycobacterium tuberculosisSigK–RskA σ–anti-σ complex". Acta Crystallographica Section D Biological Crystallography 70, nr 4 (19.03.2014): 1026–36. http://dx.doi.org/10.1107/s1399004714000121.

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The host–pathogen interactions inMycobacterium tuberculosisinfection are significantly influenced by redox stimuli and alterations in the levels of secreted antigens. The extracytoplasmic function (ECF) σ factor σKgoverns the transcription of the serodominant antigens MPT70 and MPT83. The cellular levels of σKare regulated by the membrane-associated anti-σK(RskA) that localizes σKin an inactive complex. The crystal structure ofM. tuberculosisσKin complex with the cytosolic domain of RskA (RskAcyto) revealed a disulfide bridge in the −35 promoter-interaction region of σK. Biochemical experiments reveal that the redox potential of the disulfide-forming cysteines in σKis consistent with its role as a sensor. The disulfide bond in σKinfluences the stability of the σK–RskAcytocomplex but does not interfere with σK–promoter DNA interactions. It is noted that these disulfide-forming cysteines are conserved across homologues, suggesting that this could be a general mechanism for redox-sensitive transcription regulation.

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Thakur, Krishan Gopal, Anagha Madhusudan Joshi i B. Gopal. "Structural and Biophysical Studies on Two Promoter Recognition Domains of the Extra-cytoplasmic Function σ Factor σC from Mycobacterium tuberculosis". Journal of Biological Chemistry 282, nr 7 (4.12.2006): 4711–18. http://dx.doi.org/10.1074/jbc.m606283200.

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σ factors are transcriptional regulatory proteins that bind to the RNA polymerase and dictate gene expression. The extracytoplasmic function (ECF) σ factors govern the environment dependent regulation of transcription. ECF σ factors have two domains σ2 and σ4 that recognize the -10 and -35 promoter elements. However, unlike the primary σ factor σA, the ECF σ factors lack σ3, a region that helps in the recognition of the extended -10 element and σ1.1, a domain involved in the autoinhibition of σA in the absence of core RNA polymerase. Mycobacterium tuberculosis σC is an ECF σ factor that is essential for the pathogenesis and virulence of M. tuberculosis in the mouse and guinea pig models of infection. However, unlike other ECF σ factors, σC does not appear to have a regulatory anti-σ factor located in the same operon. We also note that M. tuberculosis σC differs from the canonical ECF σ factors as it has an N-terminal domain comprising of 126 amino acids that precedes the σC2 and σC4 domains. In an effort to understand the regulatory mechanism of this protein, the crystal structures of the σC2 and σC4 domains of σC were determined. These promoter recognition domains are structurally similar to the corresponding domains of σA despite the low sequence similarity. Fluorescence experiments using the intrinsic tryptophan residues of σC2 as well as surface plasmon resonance measurements reveal that the σC2 and σC4 domains interact with each other. Mutational analysis suggests that the Pribnow box-binding region of σC2 is involved in this interdomain interaction. Interaction between the promoter recognition domains in M. tuberculosis σC are thus likely to regulate the activity of this protein even in the absence of an anti-σ factor.

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Cartagena, Alexis Jaramillo, Amy B. Banta, Nikhil Sathyan, Wilma Ross, Richard L. Gourse, Elizabeth A. Campbell i Seth A. Darst. "Structural basis for transcription activation by Crl through tethering of σS and RNA polymerase". Proceedings of the National Academy of Sciences 116, nr 38 (4.09.2019): 18923–27. http://dx.doi.org/10.1073/pnas.1910827116.

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In bacteria, a primary σ-factor associates with the core RNA polymerase (RNAP) to control most transcription initiation, while alternative σ-factors are used to coordinate expression of additional regulons in response to environmental conditions. Many alternative σ-factors are negatively regulated by anti–σ-factors. In Escherichia coli, Salmonella enterica, and many other γ-proteobacteria, the transcription factor Crl positively regulates the alternative σS-regulon by promoting the association of σS with RNAP without interacting with promoter DNA. The molecular mechanism for Crl activity is unknown. Here, we determined a single-particle cryo-electron microscopy structure of Crl-σS-RNAP in an open promoter complex with a σS-regulon promoter. In addition to previously predicted interactions between Crl and domain 2 of σS (σS2), the structure, along with p-benzoylphenylalanine cross-linking, reveals that Crl interacts with a structural element of the RNAP β′-subunit that we call the β′-clamp-toe (β′CT). Deletion of the β′CT decreases activation by Crl without affecting basal transcription, highlighting the functional importance of the Crl-β′CT interaction. We conclude that Crl activates σS-dependent transcription in part through stabilizing σS-RNAP by tethering σS2 and the β′CT. We propose that Crl, and other transcription activators that may use similar mechanisms, be designated σ-activators.

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Cavaliere, Paola, i Françoise Norel. "Recent advances in the characterization of Crl, the unconventional activator of the stress sigma factor σS/RpoS". Biomolecular Concepts 7, nr 3 (1.06.2016): 197–204. http://dx.doi.org/10.1515/bmc-2016-0006.

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AbstractThe bacterial RNA polymerase (RNAP) holoenzyme is a multisubunit core enzyme associated with a σ factor that is required for promoter-specific transcription initiation. Besides a primary σ responsible for most of the gene expression during active growth, bacteria contain alternative σ factors that control adaptive responses. A recurring strategy in the control of σ factor activity is their sequestration by anti-sigma factors that occlude the RNAP binding determinants, reducing their activity. In contrast, the unconventional transcription factor Crl binds specifically to the alternative σ factor σS/RpoS, and favors its association with the core RNAP, thereby increasing its activity. σS is the master regulator of the general stress response that protects many Gram-negative bacteria from several harmful environmental conditions. It is also required for biofilm formation and virulence of Salmonella enterica serovar Typhimurium. In this report, we discuss current knowledge on the regulation and function of Crl in Salmonella and Escherichia coli, two bacterial species in which Crl has been studied. We review recent advances in the structural characterization of the Crl-σS interaction that have led to a better understanding of this unusual mechanism of σ regulation.

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Kwak, Min-Kyu, Han-Bong Ryu, Sung-Hyun Song, Jin-Won Lee i Sa-Ouk Kang. "Anti-σ factor YlaD regulates transcriptional activity of σ factor YlaC and sporulation via manganese-dependent redox-sensing molecular switch in Bacillus subtilis". Biochemical Journal 475, nr 13 (5.07.2018): 2127–51. http://dx.doi.org/10.1042/bcj20170911.

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YlaD, a membrane-anchored anti-sigma (σ) factor of Bacillus subtilis, contains a HX3CXXC motif that functions as a redox-sensing domain and belongs to one of the zinc (Zn)-co-ordinated anti-σ factor families. Despite previously showing that the YlaC transcription is controlled by YlaD, experimental evidence of how the YlaC–YlaD interaction is affected by active cysteines and/or metal ions is lacking. Here, we showed that the Pyla promoter is autoregulated solely by YlaC. Moreover, reduced YlaD contained Zn and iron, while oxidized YlaD did not. Cysteine substitution in YlaD led to changes in its secondary structure; Cys3 had important structural functions in YlaD, and its mutation caused dissociation from YlaC, indicating the essential requirement of a HX3CXXC motif for regulating interactions of YlaC with YlaD. Analyses of the far-UV CD spectrum and metal content revealed that the addition of Mn ions to Zn–YlaD changed its secondary structure and that iron was substituted for manganese (Mn). The ylaC gene expression using βGlu activity from Pyla:gusA was observed at the late-exponential and early-stationary phase, and the ylaC-overexpressing mutant constitutively expressed gene transcripts of clpP and sigH, an important alternative σ factor regulated by ClpXP. Collectively, our data demonstrated that YlaD senses redox changes and elicits increase in Mn ion concentrations and that, in turn, YlaD-mediated transcriptional activity of YlaC regulates sporulation initiation under oxidative stress and Mn-substituted conditions by regulating clpP gene transcripts. This is the first report of the involvement of oxidative stress-responsive B. subtilis extracytoplasmic function σ factors during sporulation via a Mn-dependent redox-sensing molecular switch.

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Tamizi, Amin-Asyraf, Norliza Abu-Bakar, Aimera-Farhana Samsuddin, Lina Rozano, Rohaiza Ahmad-Redzuan i Abdul-Munir Abdul-Murad. "Characterisation and Mutagenesis Study of An Alternative Sigma Factor Gene (hrpL) from Erwinia mallotivora Reveal Its Central Role in Papaya Dieback Disease". Biology 9, nr 10 (3.10.2020): 323. http://dx.doi.org/10.3390/biology9100323.

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The alternative sigma (σ) factor E, RpoE or HrpL, has been reported to be involved in stress- and pathogenicity-related transcription initiation in Escherichia coli and many other Gram-negative bacteria, including Erwinia spp. and Pseudomonas spp. A previous study identified the hrpL/rpoE transcript as one of the significant differentially expressed genes (DEGs) during early E. mallotivora infection in papaya and those data serve as the basis of the current project. Here, the full coding DNA sequence (CDS) of hrpL from E. mallotivora (EmhrpL) was determined to be 549 bp long, and it encoded a 21.3 kDa HrpL protein that possessed two highly conserved sigma-70 (σ70) motifs—σR2 and σR4. Nucleotide sequence alignment revealed the hrpL from E. mallotivora shared high sequence similarity to rpoE/hrpL from E. tracheiphila (83%), E. pyrifoliae (81%), and E. tasmaniensis (80%). Phylogenetics analysis indicated hrpL from E. mallotivora to be monophyletic with rpoEs/hrpLs from Pantoea vagans, E. herbicola, and E. tracheiphila. Structural analysis postulated that the E. mallotivora’s alternative σ factor was non-transmembranic and was an extracytoplasmic function (ECF) protein—characteristics shared by other σ factors in different bacterial species. Notably, the protein–protein interaction (PPI) study through molecular docking suggested the σ factor could be possibly inhibited by an anti-σ. Finally, a knockout of hrpL in E. mallotivora (ΔEmhrpL) resulted in avirulence in four-month-old papaya plants. These findings have revealed that the hrpL is a necessary element in E. mallotivora pathogenicity and also predicted that the gene can be inhibited by an anti-σ.

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Anthony, Jennifer R., Jack D. Newman i Timothy J. Donohue. "Interactions Between the Rhodobacter sphaeroides ECF Sigma Factor, σ E , and its Anti-sigma Factor, ChrR". Journal of Molecular Biology 341, nr 2 (sierpień 2004): 345–60. http://dx.doi.org/10.1016/j.jmb.2004.06.018.

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Rédly, Gyula Alan, i Keith Poole. "FpvIR Control of fpvA Ferric Pyoverdine Receptor Gene Expression in Pseudomonas aeruginosa: Demonstration of an Interaction between FpvI and FpvR and Identification of Mutations in Each Compromising This Interaction". Journal of Bacteriology 187, nr 16 (15.08.2005): 5648–57. http://dx.doi.org/10.1128/jb.187.16.5648-5657.2005.

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ABSTRACT FpvR is a presumed cytoplasmic membrane-associated anti-sigma factor that controls the activities of extracytoplasmic function sigma factors PvdS and FpvI responsible for transcription of pyoverdine biosynthetic genes and the ferric pyoverdine receptor gene, fpvA, respectively. Using deletion analysis and an in vivo bacterial two-hybrid system, FpvR interaction with these σ factors was confirmed and shown to involve the cytoplasmic N-terminal 67 amino acid resides of FpvR. FpvR bound specifically to a C-terminal region of FpvI corresponding to region 4 of the σ70 family of sigma factors. FpvR and FpvI mutant proteins compromised for this interaction were generated by random and site-directed PCR mutagenesis and invariably contained secondary structure-altering proline substitution in predicted α-helices within the FpvR N terminus or FpvI region 4. PvdS was shown to bind to the same N-terminal region of FpvR, and FpvR mutations compromising FpvI binding also compromised PvdS binding, although some mutations had a markedly greater impact on PvdS binding. Apparently, these two σ factors bind to FpvR in a substantially similar but not identical fashion. Intriguingly, defects in FpvR binding correlated with a substantial drop in yields of the FpvI and to a lesser extent PvdS σ factors, suggesting that FpvR-bound FpvI and PvdS are stable while free and active sigma factor is prone to turnover.

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Paul, Deborupa, i Sanmitra Ghosh. "An overview of heat-stress response regulation in Gram-negative bacteria considering Escherichia coli as a model organism". Journal of Experimental Biology and Agricultural Sciences 10, nr 1 (28.02.2022): 190–200. http://dx.doi.org/10.18006/2022.10(1).190.200.

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Response to heat stress (HSR) is a key stress response for endurance in Escherichia coli mediated by transcriptional factor σ-32. Even though there has been extensive investigation on the contribution of proteins and chaperones in retaining protein stability in cells under stress conditions, limited information is available regarding the dynamic nature of mechanisms regulating the activity of the highly conserved heat shock proteins (Hsps). Several gene expression-based studies suggest the pivotal role of Hsp70 (DnaK) in the regulation of the expression of heat shock genes (Hsg). Direct interaction of Hsp70 with σ-32 may regulate this function in E. coli. Recent studies revealed that localization of σ-32 to the membrane interior by SRP-dependent pathway enables them to function appropriately in their role as regulators. The contributions of different cellular components including cell membrane remain unknown. Other cellular components or σ-32 interfere with polypeptides which could play a crucial role in cell survival. Sigma factor monitors and preserves outer membrane integrity of E. coli by stimulating the genes regulating outer membrane proteins (OMPs) and lipopolysaccharide (LPS) assemblage as well as through expression of small RNAs to down-regulate surplus unassembled OMPs. σ-E activity is regulated by the rate at which its membrane-encompassing anti-sigma factor, RseA is degraded. Mutations in rseA are reported to constitutively increase the sigma (E) activity that is validated at both genetic and biochemical levels. In this review, the basic mechanism of heat stress regulation in gram-negative bacteria has been elaborated using E. coli as a model organism.

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Karlinsey, Joyce E., i Kelly T. Hughes. "Genetic Transplantation: Salmonella enterica Serovar Typhimurium as a Host To Study Sigma Factor and Anti-Sigma Factor Interactions in GeneticallyIntractable Systems". Journal of Bacteriology 188, nr 1 (1.01.2006): 103–14. http://dx.doi.org/10.1128/jb.188.1.103-114.2006.

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ABSTRACT In Salmonella enterica serovar Typhimurium,σ 28 and anti-sigma factor FlgM are regulatory proteins crucial for flagellar biogenesis and motility. In this study, we used S. enterica serovar Typhimurium as an in vivo heterologous system to study σ28 and anti-σ28 interactions in organisms where genetic manipulation poses a significant challenge due to special growth requirements. The chromosomal copy of the S. enterica serovar Typhimurium σ28 structural gene fliA was exchanged with homologs of Aquifex aeolicus (an extreme thermophile) and Chlamydia trachomatis (an obligate intracellular pathogen) by targeted replacement of a tetRA element in the fliA gene location using λ-Red-mediated recombination. The S. enterica serovar Typhimurium hybrid strains showed σ28-dependent gene expression, suggesting that σ28 activities from diverse species are preserved in the heterologous host system. A. aeolicus mutants defective for σ28/FlgM interactions were also isolated in S. enterica serovar Typhimurium. These studies highlight a general strategy for analysis of protein function in species that are otherwise genetically intractable and a straightforward method of chromosome restructuring usingλ -Red-mediated recombination.

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Delumeau, Olivier, Richard J. Lewis i Michael D. Yudkin. "Protein-Protein Interactions That Regulate the Energy Stress Activation of σB in Bacillus subtilis". Journal of Bacteriology 184, nr 20 (15.10.2002): 5583–89. http://dx.doi.org/10.1128/jb.184.20.5583-5589.2002.

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ABSTRACT σB is an alternative σ factor that controls the general stress response in Bacillus subtilis. In the absence of stress, σB is negatively regulated by anti-σ factor RsbW. RsbW is also a protein kinase which can phosphorylate RsbV. When cells are stressed, RsbW binds to unphosphorylated RsbV, produced from the phosphorylated form of RsbV by two phosphatases (RsbU and RsbP) which are activated by stress. We now report the values of the Km for ATP and the Ki for ADP of RsbW (0.9 and 0.19 mM, respectively), which reinforce the idea that the kinase activity of RsbW is directly regulated in vivo by the ratio of these nucleotides. RsbW, purified as a dimer, forms complexes with RsbV and σB with different stoichiometries, i.e., RsbW2-RsbV2 and RsbW2-σB 1. As determined by surface plasmon resonance, the dissociation constants of the RsbW-RsbV and RsbW-σB interactions were found to be similar (63 and 92 nM, respectively). Nonetheless, an analysis of the complexes by nondenaturing polyacrylamide gel electrophoresis in competition assays suggested that the affinity of RsbW2 for RsbV is much higher than that for σB. The intracellular concentrations of RsbV, RsbW (as a monomer), and σB measured before stress were similar (1.5, 2.6, and 0.9 μM, respectively). After ethanol stress they all increased. The increase was greatest for RsbV, whose concentration reached 13 μM, while those of RsbW (as a monomer) and σB reached 11.8 and 4.9 μM, respectively. We conclude that the higher affinity of RsbW for RsbV than for σB, rather than a difference in the concentrations of RsbV and σB, is the driving force that is responsible for the switch of RsbW to unphosphorylated RsbV.

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Nambigari, Navaneetha. "Cancer Therapeutics: Structure-Based Drug Design of Inhibitors for a Novel Angiogenic Growth Factor". Mathematical Biology and Bioinformatics 18, nr 1 (26.03.2023): 72–88. http://dx.doi.org/10.17537/2023.18.72.

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Angiogenesis, the formation of new blood vessels, is a critical and rate-limiting tumor growth step controlled by pro-angiogenic factors and specific inhibitors. Tumor angiogenesis is essential for cancer progression and metastasis. Platelet growth factors (PDGF) and their receptors (PDGFR) are associated with tumor angiogenesis through overexpression of PDGF. Inhibition of PDGF and its signaling pathway is a new approach to the discovery of anticancer therapeutic agents. The present study focuses on the PDGF-C protein in the identification of novel anti-angiogenic compounds. MODELLER 9.10 software allows users to create and refine a 3D homology model of the PDGF-C protein (345 a.a. length). Secondary structure analysis of the 3D energy model reveals 16 β sheets held together by four cation–π and one π–σ interactions, and three salt bridges. The quality of the model is assessed using the Ramachandran plot (90 percent amino acids in the favorable region) and the ProSA server (Z-score = –2.28). Active site residues are identified using Castp, QSite search engine, site map, and protein docking of the protein to its receptor. In addition, virtual screening is performed at the active site using the Glide module of the Schrodinger Suite. Glide score, glide energy and ADME are being measured to discover new benefits of pyrazolone and pyrrolidine-2,3-dione scaffolds as potent PDGF-C antagonists for anti-angiogenic cancer chemotherapy drugs.

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Rijken, Th A., M. M. Nagels i Y. Yamamoto. "NIJMEGEN BARYON-BARYON INTERACTIONS FOR S = -1, -2 SYSTEMS". International Journal of Modern Physics E 19, nr 12 (grudzień 2010): 2418–27. http://dx.doi.org/10.1142/s0218301310016892.

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We present and discuss the most recent version of the extended-soft-core (ESC) interactions. The ESC-model describes the nucleon-nucleon ( NN ), hyperon-nucleon ( YN ), and hyperon-hyperon ( YY ), in terms of meson-exchanges using (broken) SUF(3)-symmetry. In this approach to baryon-baryon ( BB ) the dynamics is derived from (i) one-boson-exchanges (OBE), (ii) two-meson-exchanges (TME), and (iii) meson-pair-exchanges (MPE), (iv) gluon-exchanges, and (v) quark-core effects. In the OBE-sector, a special feature is the importance of the axial-vector meson potentials, and the inclusion of a zero in the scalar- and axial- meson form-factors. Novelties are the inclusion of (a) odderon-exchange, and (b) special pronounced effects of the appearance of forbidden six-quark configurations. With these ingredients, a rather flexible dynamical framework is constructed. Namely, it appeared feasible to keep the parameters of the model in reasonable accordance with the predictions of the 3P0 quark-pair-creation model (QPC). This is the case for the meson- and meson-pair-baryon coupling constants and the F/(F + D)-ratio's as well. The NN , YN , and YY results for this model are rather promising. In particular, we improved the ΛN spin-orbit interaction greatly by the inclusion of (a) the Brown, Downs, and Iddings anti-symmetric spin-orbit potentials, and (b) new corrections to the MPE-potentials. Also, the special quark-core effects provide ample repulsion in the Σ+p(3S1,T = 3/2)- and ΣN(1S0,T = 1/2)-channels. The new version of the ESC-model reported here will be referred to as ESC07 henceforth.

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Dehbi, Mohammed, Gregory Moeck, Francis F. Arhin, Pascale Bauda, Dominique Bergeron, Tony Kwan, Jing Liu, John McCarty, Michael DuBow i Jerry Pelletier. "Inhibition of Transcription in Staphylococcus aureus by a Primary Sigma Factor-Binding Polypeptide from Phage G1". Journal of Bacteriology 191, nr 12 (17.04.2009): 3763–71. http://dx.doi.org/10.1128/jb.00241-09.

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ABSTRACT The primary sigma factor of Staphylococcus aureus, σSA, regulates the transcription of many genes, including several essential genes, in this bacterium via specific recognition of exponential growth phase promoters. In this study, we report the existence of a novel staphylococcal phage G1-derived growth inhibitory polypeptide, referred to as G1ORF67, that interacts with σSA both in vivo and in vitro and regulates its activity. Delineation of the minimal domain of σSA that is required for its interaction with G1ORF67 as amino acids 294 to 360 near the carboxy terminus suggests that the G1 phage-encoded anti-σ factor may occlude the −35 element recognition domain of σSA. As would be predicted by this hypothesis, the G1ORF67 polypeptide abolished both RNA polymerase core-dependent binding of σSA to DNA and σSA-dependent transcription in vitro. While G1ORF67 profoundly inhibits transcription when expressed in S. aureus cells in mode of action studies, our finding that G1ORF67 was unable to inhibit transcription when expressed in Escherichia coli concurs with its inability to inhibit transcription by the E. coli holoenzyme in vitro. These features demonstrate the selectivity of G1ORF67 for S. aureus RNA polymerase. We predict that G1ORF67 is one of the central polypeptides in the phage G1 strategy to appropriate host RNA polymerase and redirect it to phage reproduction.

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Maillard, Antoine P., Eric Girard, Widade Ziani, Isabelle Petit-Härtlein, Richard Kahn i Jacques Covès. "The Crystal Structure of the Anti-σ Factor CnrY in Complex with the σ Factor CnrH Shows a New Structural Class of Anti-σ Factors Targeting Extracytoplasmic Function σ Factors". Journal of Molecular Biology 426, nr 12 (czerwiec 2014): 2313–27. http://dx.doi.org/10.1016/j.jmb.2014.04.003.

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McGuffie, Bryan A., Isabelle Vallet-Gely i Simon L. Dove. "σ Factor and Anti-σ Factor That Control Swarming Motility and Biofilm Formation in Pseudomonas aeruginosa". Journal of Bacteriology 198, nr 5 (30.11.2015): 755–65. http://dx.doi.org/10.1128/jb.00784-15.

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ABSTRACTPseudomonas aeruginosais capable of causing a variety of acute and chronic infections. Here, we provide evidence thatsbrR(PA2895), a gene previously identified as required during chronicP. aeruginosarespiratory infection, encodes an anti-σ factor that inhibits the activity of its cognate extracytoplasmic-function σ factor, SbrI (PA2896). Bacterial two-hybrid analysis identified an N-terminal region of SbrR that interacts directly with SbrI and that was sufficient for inhibition of SbrI-dependent gene expression. We show that SbrI associates with RNA polymerasein vivoand identify the SbrIR regulon. In cells lacking SbrR, the SbrI-dependent expression ofmuiAwas found to inhibit swarming motility and promote biofilm formation. Our findings reveal SbrR and SbrI as a novel set of regulators of swarming motility and biofilm formation inP. aeruginosathat mediate their effects throughmuiA, a gene not previously known to influence surface-associated behaviors in this organism.IMPORTANCEThis study characterizes a σ factor/anti-σ factor system that reciprocally regulates the surface-associated behaviors of swarming motility and biofilm formation in the opportunistic pathogenPseudomonas aeruginosa. We present evidence that SbrR is an anti-σ factor specific for its cognate σ factor, SbrI, and identify the SbrIR regulon inP. aeruginosa. We find that cells lacking SbrR are severely defective in swarming motility and exhibit enhanced biofilm formation. Moreover, we identifymuiA(PA1494) as the SbrI-dependent gene responsible for mediating these effects. SbrIR have been implicated in virulence and in responding to antimicrobial and cell envelope stress. SbrIR may therefore represent a stress response system that influences the surface behaviors ofP. aeruginosaduring infection.

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Campbell, Elizabeth A., Shoko Masuda, Jing L. Sun, Oriana Muzzin, C. Anders Olson, Sheng Wang i Seth A. Darst. "Crystal Structure of the Bacillus stearothermophilus Anti-σ Factor SpoIIAB with the Sporulation σ Factor σF". Cell 108, nr 6 (marzec 2002): 795–807. http://dx.doi.org/10.1016/s0092-8674(02)00662-1.

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Griffiths-Jones, D., Y. Sylvestre Garcia, D. Ryder, J. Pauling, F. Hall, P. Lanyon, J. Mason, C. P. Denton i A. Herrick. "POS0850 A PHASE II RANDOMISED CONTROLLED TRIAL OF ORAL PREDNISOLONE IN EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (PRedSS)". Annals of the Rheumatic Diseases 81, Suppl 1 (23.05.2022): 717.2–718. http://dx.doi.org/10.1136/annrheumdis-2022-eular.694.

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BackgroundA highly controversial question is whether or not corticosteroids should be prescribed for patients with early diffuse cutaneous systemic sclerosis (dcSSc). Although the painful and disabling features of early dcSSc (including tight itchy skin, contractures, fatigue) have an inflammatory basis and are likely to respond to corticosteroids, corticosteroids are a risk factor for potentially life-threatening scleroderma renal crisis.ObjectivesOur aim was to examine safety and efficacy of moderate dose prednisolone in patients with early dcSSc. Specific objectives were to evaluate whether moderate dose prednisolone reduced pain and disability, and improved skin score, and whether prednisolone was safe with particular reference to renal functionMethodsPRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label because of the Covid-19 pandemic. Patients were randomised to receive either moderate dose prednisolone (approximately 0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. The co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, anxiety and depression, fatigue and helplessness. 72 participants randomised 1:1 were planned and anticipated to yield 60 evaluable, giving over 80% power for each co-primary outcome in ANCOVA analyses [assumptions; HAQ-DI (α = 0.025, δ = -0.6, σ = 0.9, ρ = 0.6), mRSS (α = 0.025, δ = -5.5, σ = 8.2, ρ = 0.6)]. Mixed Models for Repeated Measures (week 6, month 3, month 6) were fitted with covariates trial arm, baseline score, anti-Scl-70 and their interactions with time point. An unstructured covariance matrix was assumed with the primary focus being the trial arm effect at 3 months.ResultsThe study terminated early due to the Covid-19 pandemic and consequently did not meet the recruitment target of 72 patients. Thirty-five patients (Table 1) were randomised (17 to prednisolone and 18 to placebo/control, 25 during the double-blind phase), of whom 34 completed the 3 month assessment. The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was -0.10 (97.5% CI -0.29 to 0.10), p=0.25, and in mRSS -3.90 (97.5% CI -8.83 to 1.03), p=0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced less pain, helplessness and anxiety than control patients at 3 months: mean difference in pain scores -0.49, 95%CI (-0.93 to -0.06), p=0.027, in Hospital Anxiety and Depression (HADS) anxiety scores -2.05, 95%CI (-3.73 to -0.37), p=0.018, and in helplessness scores -1.54, 95%CI (-3.01 to -0.07), p=0.040. There were no renal crises.Table 1.Baseline characteristics of patients by treatment allocationCharacteristicPrednisolone (n=17)Control (n=18)Age (years)52.7 (14.0)55.3 (12.7)Female n (%)10 (59)9 (50)Duration of skin thickening (years)1.6 (0.8)1.7 (0.8)Anti-topoisomerase-1 n (%)5 (29)6 (33)Anti-RNA polymerase III n (%)6 (35)8 (44)HAQ-DI1.6 (0.8)1.7 (0.7)mRSS18.8 (7.9)23.5 (8.6)Values are mean (standard deviation) unless stated otherwiseConclusionPRedSS exemplified the challenges of running a clinical trial of an investigational medicinal product potentially associated with increased infection risk during the Covid-19 pandemic. Because PRedSS was terminated prior to target recruitment, it was underpowered, and any conclusions have to be extremely cautious. Although PRedSS suggested some benefit from moderate dose prednisolone, the small sample indicates the need for a further randomised trial.References[1]Herrick AL et al. Clinical trial protocol: PRednisolone in early diffuse cutaneous Systemic Sclerosis. J Scleroderma Rel Disord 2021; 6: 146-153.AcknowledgementsThis work was funded by Versus ArthritisDisclosure of InterestsDeb Griffiths-Jones: None declared, Yvonne Sylvestre Garcia: None declared, David Ryder: None declared, John Pauling Speakers bureau: Janssen, Consultant of: Janssen, Boehringer Ingelheim, Permeatus Inc, Sojournix Pharma and Astra Zeneca, Frances Hall Consultant of: Sobi, Roche, Grant/research support from: Alexion, Lilly, BMS, Actelion, Sobi, Peter Lanyon Grant/research support from: Vifor pharma, Justin Mason Consultant of: Pfizer, Novartis, Janssen and Roche., Christopher P Denton Speakers bureau: Janssen, Boehringer Ingelheim, Consultant of: GSK, Boehringer Ingelheim, CSL Behring, Corbus, Roche, Gesynta, Grant/research support from: Servier, GSK, Arxx Therapeutics, Horizon, Ariane Herrick Speakers bureau: Janssen, Consultant of: Arena, Boehringer-Ingelheim, Camurus, CSL-Behring, Gesynta, Grant/research support from: Gesynta

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Sorenson, Margareta K., Soumya S. Ray i Seth A. Darst. "Crystal Structure of the Flagellar σ/Anti-σ Complex σ28/FlgM Reveals an Intact σ Factor in an Inactive Conformation". Molecular Cell 14, nr 1 (kwiecień 2004): 127–38. http://dx.doi.org/10.1016/s1097-2765(04)00150-9.

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Lachowicz, Mirosław, Henryk Leszczyński i Elżbieta Puźniakowska–Gałuch. "Diffusive and Anti-Diffusive Behavior for Kinetic Models of Opinion Dynamics". Symmetry 11, nr 8 (8.08.2019): 1024. http://dx.doi.org/10.3390/sym11081024.

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In the present paper, we study a class of nonlinear integro-differential equations of a kinetic type describing the dynamics of opinion for two types of societies: conformist ( σ = 1 ) and anti-conformist ( σ = - 1 ). The essential role is played by the symmetric nature of interactions. The class may be related to the mesoscopic scale of description. This means that we are going to statistically describe an individual state of an agent of the system. We show that the corresponding equations result at the macroscopic scale in two different pictures: anti-diffusive ( σ = 1 ) and diffusive ( σ = - 1 ). We provide a rigorous result on the convergence. The result captures the macroscopic behavior resulting from the mesoscopic one. In numerical examples, we observe both unipolar and bipolar behavior known in political sciences.

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Werstiuk, Nick Henry, i Jiangong Ma. "An AM1 calculational study of the Diels–Alder addition of maleic anhydride to C5-substituted pentamethylcyclopentadienes and 2,5-dimethylthiophene oxide. An attempt to ascertain the factors controlling the π-facial selectivities and relative reactivities". Canadian Journal of Chemistry 72, nr 12 (1.12.1994): 2493–505. http://dx.doi.org/10.1139/v94-316.

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The Diels–Alder reactions of maleic anhydride (1) with a group of C5-substituted cyclopentadienes and 2,5-dimethylthiophene oxide (5) have been studied with the semi-empirical method AM1. We find that the facial selectivities and relative reactivities found experimentally for six dienes (2a–2f) are accurately reproduced at this level of theory. The results of the calculational study provide no concrete support for the proposal that σ–σ* hyperconjugation in the transition state – an interaction between a σ bond at C5 of the cyclopentadiene and the incipient σ bonds anti to it (the Cieplak effect) – is the major source of the syn facial selectivity observed for 2a–2d. In addition, the relative reactivities and facial selectivities are predicted for a number of cyclopentadienes which will be synthesized and studied experimentally.

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Hubin, Elizabeth A., Aline Tabib-Salazar, Laurence J. Humphrey, Joshua E. Flack, Paul Dominic B. Olinares, Seth A. Darst, Elizabeth A. Campbell i Mark S. Paget. "Structural, functional, and genetic analyses of the actinobacterial transcription factor RbpA". Proceedings of the National Academy of Sciences 112, nr 23 (26.05.2015): 7171–76. http://dx.doi.org/10.1073/pnas.1504942112.

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Gene expression is highly regulated at the step of transcription initiation, and transcription activators play a critical role in this process. RbpA, an actinobacterial transcription activator that is essential inMycobacterium tuberculosis(Mtb), binds selectively to group 1 and certain group 2 σ-factors. To delineate the molecular mechanism of RbpA, we show that theMtbRbpA σ-interacting domain (SID) and basic linker are sufficient for transcription activation. We also present the crystal structure of theMtbRbpA-SID in complex with domain 2 of the housekeeping σ-factor, σA. The structure explains the basis of σ-selectivity by RbpA, showing that RbpA interacts with conserved regions of σAas well as the nonconserved region (NCR), which is present only in housekeeping σ-factors. Thus, the structure is the first, to our knowledge, to show a protein interacting with the NCR of a σ-factor. We confirm the basis of selectivity and the observed interactions using mutagenesis and functional studies. In addition, the structure allows for a model of the RbpA-SID in the context of a transcription initiation complex. Unexpectedly, the structural modeling suggests that RbpA contacts the promoter DNA, and we present in vivo and in vitro studies supporting this finding. Our combined data lead to a better understanding of the mechanism of RbpA function as a transcription activator.

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Guzina, Jelena, i Marko Djordjevic. "Promoter Recognition by Extracytoplasmic Function σ Factors: Analyzing DNA and Protein Interaction Motifs". Journal of Bacteriology 198, nr 14 (2.05.2016): 1927–38. http://dx.doi.org/10.1128/jb.00244-16.

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ABSTRACTExtracytoplasmicfunction (ECF) σ factors are the largest and the most diverse group of alternative σ factors, but their mechanisms of transcription are poorly studied. This subfamily is considered to exhibit a rigid promoter structure and an absence of mixing and matching; both −35 and −10 elements are considered necessary for initiating transcription. This paradigm, however, is based on very limited data, which bias the analysis of diverse ECF σ subgroups. Here we investigate DNA and protein recognition motifs involved in ECF σ factor transcription by a computational analysis of canonical ECF subfamily members, much less studied ECF σ subgroups, and the group outliers, obtained from recently sequenced bacteriophages. The analysis identifies an extended −10 element in promoters for phage ECF σ factors; a comparison with bacterial σ factors points to a putative 6-amino-acid motif just C-terminal of domain σ2, which is responsible for the interaction with the identified extension of the −10 element. Interestingly, a similar protein motif is found C-terminal of domain σ2in canonical ECF σ factors, at a position where it is expected to interact with a conserved motif further upstream of the −10 element. Moreover, the phiEco32 ECF σ factor lacks a recognizable −35 element and σ4domain, which we identify in a homologous phage, 7-11, indicating that the extended −10 element can compensate for the lack of −35 element interactions. Overall, the results reveal greater flexibility in promoter recognition by ECF σ factors than previously recognized and raise the possibility that mixing and matching also apply to this group, a notion that remains to be biochemically tested.IMPORTANCEECF σ factors are the most numerous group of alternative σ factors but have been little studied. Their promoter recognition mechanisms are obscured by the large diversity within the ECF σ factor group and the limited similarity with the well-studied housekeeping σ factors. Here we extensively compare bacterial and bacteriophage ECF σ factors and their promoters in order to infer DNA and protein recognition motifs involved in transcription initiation. We predict a more flexible promoter structure than is recognized by the current paradigm, which assumes rigidness, and propose that ECF σ promoter elements may complement (mix and match with) each other's strengths. These results warrant the refocusing of research efforts from the well-studied housekeeping σ factors toward the physiologically highly important, but insufficiently understood, alternative σ factors.

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Yamato, Takehiko, Hideo Kamimura i Hirohisa Tsuzuki. "ipso-Nitration of tert-butyl[n.2]metacyclophanes; through-space electronic interactions between two benzene rings". Canadian Journal of Chemistry 76, nr 7 (1.07.1998): 997–1005. http://dx.doi.org/10.1139/v98-111.

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The selective introduction of one or two nitro groups by direct replacement of tert-butyl groups via the ipso aromatic nitration of the meta-bridged aromatic compounds having two arene rings is described. The ipso-nitration at the tert-butyl groups of syn- and anti-di-tert-butyl-dimethoxy[n.2]metacyclophanes 1 is attributed to the highly activated character of the aryl ring and the increased stabilization of a σ-complex intermediate arising from the dienone-type σ-complex intermediate possible in the case of an internally methoxy substituent. However, only one tert-butyl group is ipso-nitrated in the mild reaction conditions such as copper(II) nitrate in an acetic anhydride solution because of deactivation of the second aromatic ring by the introduced nitro group. A first σ-complex intermediate would be stabilized by two types of the through-space electronic interaction, i.e., face-to-face overlapping and intra-annular interaction with the opposing benzene ring, thus accelerating the reaction. The higher yields of mononitrated product are obtained in syn-conformer than in anti-conformer. Therefore, face-to-face overlapping might be much more favourable to stabilize the first σ-complex intermediate than the intra-annular interaction. On the other hand, nitration of 1 with fuming nitric acid afforded the two-fold ipso-nitration product 3 in quantitative yield. Thus, the number of ipso-nitration at the tert-butyl groups of 1 was strongly affected by the reactivity of the nitration reagent.Key words: cyclophanes, electrophilic aromatic substitutions, ipso-nitration, σ-complex intermediates, through-space electronic interactions.

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Campbell, Elizabeth A., i Seth A. Darst. "The anti-σ factor SpoIIAB forms a 2:1 complex with σF, contacting multiple conserved regions of the σ factor". Journal of Molecular Biology 300, nr 1 (czerwiec 2000): 17–28. http://dx.doi.org/10.1006/jmbi.2000.3838.

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Ho, Theresa D., i Craig D. Ellermeier. "PrsW Is Required for Colonization, Resistance to Antimicrobial Peptides, and Expression of Extracytoplasmic Function σ Factors in Clostridium difficile". Infection and Immunity 79, nr 8 (31.05.2011): 3229–38. http://dx.doi.org/10.1128/iai.00019-11.

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ABSTRACTClostridium difficileis an anaerobic, Gram-positive, spore-forming, opportunistic pathogen that is the most common cause of hospital-acquired infectious diarrhea. In numerous pathogens, stress response mechanisms are required for survival within the host. Extracytoplasmic function (ECF) σ factors are a major family of signal transduction systems, which sense and respond to extracellular stresses. We have identified threeC. difficileECF σ factors. These ECF σ factors, CsfT, CsfU, and CsfV, induce their own expressions and are negatively regulated by their cognate anti-σ factors, RsiT, RsiU, and RsiV, respectively. The levels of expression of these ECF σ factors increase following exposure to the antimicrobial peptides bacitracin and/or lysozyme. The expressions of many ECF σ factors are controlled by site 1 and site 2 proteases, which cleave anti-σ factors. Using a retargeted group II intron, we generated aC. difficilemutation inprsW, a putative site 1 protease. TheC. difficile prsWmutant exhibited decreased levels of expression of CsfT and CsfU but not of CsfV. When expressed in a heterologous host,C. difficilePrsW was able to induce the degradation of RsiT but not of RsiU. When theprsWmutant was tested in competition assays against its isogenic parent in the hamster model ofC. difficileinfection, we found that theprsWmutant was 30-fold less virulent than the wild type. TheprsWmutant was also significantly more sensitive to bacitracin and lysozyme than the wild type inin vitrocompetition assays. Taken together, these data suggest that PrsW likely regulates the activation of the ECF σ factor CsfT inC. difficileand controls the resistance ofC. difficileto antimicrobial peptides that are important for survival in the host.

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Kodgire, Prashant, i K. Krishnamurthy Rao. "hag expression in Bacillus subtilis is both negatively and positively regulated by ScoC". Microbiology 155, nr 1 (1.01.2009): 142–49. http://dx.doi.org/10.1099/mic.0.021899-0.

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In Bacillus subtilis, motility and chemotaxis require the expression of hag, which encodes flagellin. This gene is transcribed by the σ D form of RNA polymerase and is regulated by a group of proteins called transition state regulators (TSRs). Our studies show that hag transcription is negatively regulated by the transition state regulator ScoC, by binding to its promoter. Furthermore, ScoC, indirectly, also positively regulates hag by increasing the availability of σ D by downregulating the levels of the anti-σ D-factor FlgM. We further show that the positive regulation by ScoC predominates over the negative regulation.

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Kallifidas, Dimitris, Derek Thomas, Phillip Doughty i Mark S. B. Paget. "The σ R regulon of Streptomyces coelicolor A3(2) reveals a key role in protein quality control during disulphide stress". Microbiology 156, nr 6 (1.06.2010): 1661–72. http://dx.doi.org/10.1099/mic.0.037804-0.

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Diamide is an artificial disulphide-generating electrophile that mimics an oxidative shift in the cellular thiol–disulphide redox state (disulphide stress). The Gram-positive bacterium Streptomyces coelicolor senses and responds to disulphide stress through the σ R–RsrA system, which comprises an extracytoplasmic function (ECF) sigma factor and a redox-active anti-sigma factor. Known targets that aid in the protection and recovery from disulphide stress include the thioredoxin system and genes involved in producing the major thiol buffer mycothiol. Here we determine the global response to diamide in wild-type and sigR mutant backgrounds to understand the role of σ R in this response and to reveal additional regulatory pathways that allow cells to cope with disulphide stress. In addition to thiol oxidation, diamide was found to cause protein misfolding and aggregation, which elicited the induction of the HspR heat-shock regulon. Although this response is σ R-independent, σ R does directly control Clp and Lon ATP-dependent AAA(+) proteases, which may partly explain the reduced ability of a sigR mutant to resolubilize protein aggregates. σ R also controls msrA and msrB methionine sulphoxide reductase genes, implying that σ R–RsrA is responsible for the maintenance of both cysteine and methionine residues during oxidative stress. This work shows that the σ R–RsrA system plays a more significant role in protein quality control than previously realized, and emphasizes the importance of controlling the cellular thiol–disulphide redox balance.

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Masuda, Shoko, Katsuhiko S. Murakami, Sheng Wang, C. Anders Olson, Jill Donigian, Fred Leon, Seth A. Darst i Elizabeth A. Campbell. "Crystal Structures of the ADP and ATP Bound Forms of the Bacillus Anti-σ Factor SpoIIAB in Complex with the Anti-anti-σ SpoIIAA". Journal of Molecular Biology 340, nr 5 (lipiec 2004): 941–56. http://dx.doi.org/10.1016/j.jmb.2004.05.040.

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Paudel, Hari Ram, Lucas José Karas i Judy I.-Chia Wu. "On the reciprocal relationship between σ-hole bonding and (anti)aromaticity gain in ketocyclopolyenes". Organic & Biomolecular Chemistry 18, nr 27 (2020): 5125–29. http://dx.doi.org/10.1039/d0ob01076f.

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σ-Hole bonding interactions (e.g., tetrel, pnictogen, chalcogen, and halogen bonding) can polarize π-electrons to enhance cyclic [4n] π-electron delocalization (i.e., antiaromaticity gain) or cyclic [4n + 2] π-electron delocalization (i.e., aromaticity gain).

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Ledermann, Raphael, Ilka Bartsch, Barbara Müller, Janine Wülser i Hans-Martin Fischer. "A Functional General Stress Response of Bradyrhizobium diazoefficiens Is Required for Early Stages of Host Plant Infection". Molecular Plant-Microbe Interactions® 31, nr 5 (maj 2018): 537–47. http://dx.doi.org/10.1094/mpmi-11-17-0284-r.

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Phylogenetically diverse bacteria respond to various stress conditions by mounting a general stress response (GSR) resulting in the induction of protection or damage repair functions. In α-proteobacteria, the GSR is induced by a regulatory cascade consisting of the extracytoplasmic function (ECF) σ factor σEcfG, its anti-σ factor NepR, and the anti-anti-σ factor PhyR. We have reported previously that σEcfG and PhyR of Bradyrhizobium diazoefficiens (formerly named Bradyrhizobium japonicum), the nitrogen-fixing root nodule symbiont of soybean and related legumes, are required for efficient symbiosis; however, the precise role of the GSR remained undefined. Here, we analyze the symbiotic defects of a B. diazoefficiens mutant lacking σEcfG by comparing distinct infection stages of enzymatically or fluorescently tagged wild-type and mutant bacteria. Although root colonization and root hair curling were indistinguishable, the mutant was not competitive, and showed delayed development of emerging nodules and only a few infection threads. Consequently, many of the mutant-induced nodules were aborted, empty, or partially colonized. Congruent with these results, we found that σEcfG was active in bacteria present in root-hair-entrapped microcolonies and infection threads but not in root-associated bacteria and nitrogen-fixing bacteroids. We conclude that GSR-controlled functions are crucial for synchronization of infection thread formation, colonization, and nodule development.

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Fang, Chengli, Lingting Li, Liqiang Shen, Jing Shi, Sheng Wang, Yu Feng i Yu Zhang. "Structures and mechanism of transcription initiation by bacterial ECF factors". Nucleic Acids Research 47, nr 13 (27.05.2019): 7094–104. http://dx.doi.org/10.1093/nar/gkz470.

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Abstract Bacterial RNA polymerase (RNAP) forms distinct holoenzymes with extra-cytoplasmic function (ECF) σ factors to initiate specific gene expression programs. In this study, we report a cryo-EM structure at 4.0 Å of Escherichia coli transcription initiation complex comprising σE—the most-studied bacterial ECF σ factor (Ec σE-RPo), and a crystal structure at 3.1 Å of Mycobacterium tuberculosis transcription initiation complex with a chimeric σH/E (Mtb σH/E-RPo). The structure of Ec σE-RPo reveals key interactions essential for assembly of E. coli σE-RNAP holoenzyme and for promoter recognition and unwinding by E. coli σE. Moreover, both structures show that the non-conserved linkers (σ2/σ4 linker) of the two ECF σ factors are inserted into the active-center cleft and exit through the RNA-exit channel. We performed secondary-structure prediction of 27,670 ECF σ factors and find that their non-conserved linkers probably reach into and exit from RNAP active-center cleft in a similar manner. Further biochemical results suggest that such σ2/σ4 linker plays an important role in RPo formation, abortive production and promoter escape during ECF σ factors-mediated transcription initiation.

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Stockwell, S. B., L. Reutimann i M. L. Guerinot. "A Role for Bradyrhizobium japonicum ECF16 Sigma Factor EcfS in the Formation of a Functional Symbiosis with Soybean". Molecular Plant-Microbe Interactions® 25, nr 1 (styczeń 2012): 119–28. http://dx.doi.org/10.1094/mpmi-07-11-0188.

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Alternative sigma (σ) factors, proteins that recruit RNA polymerase core enzyme to target promoters, are one mechanism by which bacteria transcriptionally regulate groups of genes in response to environmental stimuli. A class of σ70 proteins, termed extracytoplasmic function (ECF) σ factors, are involved in cellular processes such as bacterial stress responses and virulence. Here, we describe an ECF16 σ factor, EcfS (Blr4928) from the gram-negative soil bacterium Bradyrhizobium japonicum USDA110, that plays a critical role in the establishment of a functional symbiosis with soybean. Nonpolar insertional mutants of ecfS form immature nodules that do not fix nitrogen, a defect that can be successfully complemented by expression of ecfS. Overexpression of the cocistronic gene, tmrS (blr4929), phenocopies the ecfS mutant in planta and, therefore, we propose that TmrS is a negative regulator of EcfS, a determination consistent with the prediction that it encodes an anti-σ factor. Microarray analysis of the ecfS mutant and tmrS overexpressor was used to identify 40 transcripts misregulated in both strains. These transcripts primarily encode proteins of unknown and transport-related functions and may provide insights into the symbiotic defect in these strains.

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Wecke, Tina, Birgit Veith, Armin Ehrenreich i Thorsten Mascher. "Cell Envelope Stress Response in Bacillus licheniformis: Integrating Comparative Genomics, Transcriptional Profiling, and Regulon Mining To Decipher a Complex Regulatory Network". Journal of Bacteriology 188, nr 21 (25.08.2006): 7500–7511. http://dx.doi.org/10.1128/jb.01110-06.

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ABSTRACT The envelope is an essential structure of the bacterial cell, and maintaining its integrity is a prerequisite for survival. To ensure proper function, transmembrane signal-transducing systems, such as two-component systems (TCS) and extracytoplasmic function (ECF) σ factors, closely monitor its condition and respond to harmful perturbations. Both systems consist of a transmembrane sensor protein (histidine kinase or anti-σ factor, respectively) and a corresponding cytoplasmic transcriptional regulator (response regulator or σ factor, respectively) that mediates the cellular response through differential gene expression. The regulatory network of the cell envelope stress response is well studied in the gram-positive model organism Bacillus subtilis. It consists of at least two ECF σ factors and four two-component systems. In this study, we describe the corresponding network in a close relative, Bacillus licheniformis. Based on sequence homology, domain architecture, and genomic context, we identified five TCS and eight ECF σ factors as potential candidate regulatory systems mediating cell envelope stress response in this organism. We characterized the corresponding regulatory network by comparative transcriptomics and regulon mining as an initial screening tool. Subsequent in-depth transcriptional profiling was applied to define the inducer specificity of each identified cell envelope stress sensor. A total of three TCS and seven ECF σ factors were shown to be induced by cell envelope stress in B. licheniformis. We noted a number of significant differences, indicative of a regulatory divergence between the two Bacillus species, in addition to the expected overlap in the respective responses.

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Alhadlaq, Meshari Ahmed, Jeffrey Green i Bassam K. Kudhair. "Analysis of Kytococcus sedentarius Strain Isolated from a Dehumidifier Operating in a University Lecture Theatre: Systems for Aerobic Respiration, Resisting Osmotic Stress, and Sensing Nitric Oxide". Microbial Physiology 31, nr 2 (2021): 135–45. http://dx.doi.org/10.1159/000512751.

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A strain of Kytococcus sedentarius was isolated from a dehumidifier operating in a university lecture theatre. Genome analysis and phenotypic characterisation showed that this strain, K. sedentarius MBB13, was a moderately halotolerant aerobe with a branched aerobic electron transport chain and genes that could contribute to erythromycin resistance. The major compatible solute was glycine betaine, with ectoine and proline being deployed at higher osmolarities. Actinobacteria possess multiple WhiB-like (Wbl) regulatory proteins, and K. sedentarius MBB13 has four (WhiB1, WhiB2, WhiB3, and WhiB7). Wbls are iron-sulfur proteins that regulate gene expression through interactions with RNA polymerase sigma factors and/or other regulatory proteins. Bacterial two-hybrid analyses suggested that WhiB1 and WhiB2, but not WhiB3 and WhiB7, interact with the C-terminal domain of the major sigma factor, σA; no interaction was detected between any of the Wbl proteins and the only alternative sigma factors, σB, σH, or σJ. The interaction between σA and WhiB1 or WhiB2 was disrupted in a heterologous system under growth conditions that produce nitric oxide and the iron-sulfur clusters of the isolated WhiB1 and WhiB2 proteins reacted with nitric oxide. Thus, K. sedentarius strain exhibits the major phenotypic characteristics of the type strain and a comprehensive examination of the interactions between its four Wbl proteins and four sigma factors suggested that the Wbl proteins all operate through interaction with σA.

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Torres-Gómez, Héctor, Constantin Daniliuc, Dirk Schepmann, Erik Laurini, Sabrina Pricl i Bernhard Wünsch. "Propellanes as Rigid Scaffolds for the Stereodefined Attachment of σ-Pharmacophoric Structural Elements to Achieve σ Affinity". International Journal of Molecular Sciences 22, nr 11 (26.05.2021): 5685. http://dx.doi.org/10.3390/ijms22115685.

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Following the concept of conformationally restriction of ligands to achieve high receptor affinity, we exploited the propellane system as rigid scaffold allowing the stereodefined attachment of various substituents. Three types of ligands were designed, synthesized and pharmacologically evaluated as σ1 receptor ligands. Propellanes with (1) a 2-methoxy-5-methylphenylcarbamate group at the “left” five-membered ring and various amino groups on the “right” side; (2) benzylamino or analogous amino moieties on the “right” side and various substituents at the left five-membered ring and (3) various urea derivatives at one five-membered ring were investigated. The benzylamino substituted carbamate syn,syn-4a showed the highest σ1 affinity within the group of four stereoisomers emphasizing the importance of the stereochemistry. The cyclohexylmethylamine 18 without further substituents at the propellane scaffold revealed unexpectedly high σ1 affinity (Ki = 34 nM) confirming the relevance of the bioisosteric replacement of the benzylamino moiety by the cyclohexylmethylamino moiety. Reduction of the distance between the basic amino moiety and the “left” hydrophobic region by incorporation of the amino moiety into the propellane scaffold resulted in azapropellanes with particular high σ1 affinity. As shown for the propellanamine 18, removal of the carbamate moiety increased the σ1 affinity of 9a (Ki = 17 nM) considerably. Replacement of the basic amino moiety by H-bond forming urea did not lead to potent σ ligands. According to molecular dynamics simulations, both azapropellanes anti-5 and 9a as well as propellane 18 adopt binding poses at the σ1 receptor, which result in energetic values correlating well with their different σ1 affinities. The affinity of the ligands is enthalpy driven. The additional interactions of the carbamate moiety of anti-5 with the σ1 receptor protein cannot compensate the suboptimal orientations of the rigid propellane and its N-benzyl moiety within the σ1 receptor-binding pocket, which explains the higher σ1 affinity of the unsubstituted azapropellane 9a.

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38

Hastie, Jessica L., Kyle B. Williams, Carolina Sepúlveda, Jon C. Houtman, Katrina T. Forest i Craig D. Ellermeier. "Evidence of a Bacterial Receptor for Lysozyme: Binding of Lysozyme to the Anti-σ Factor RsiV Controls Activation of the ECF σ Factor σV". PLoS Genetics 10, nr 10 (2.10.2014): e1004643. http://dx.doi.org/10.1371/journal.pgen.1004643.

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Meng, Ying, i Qiman Liu. "New Insights into Adsorption Properties of the Tubular Au26 from AIMD Simulations and Electronic Interactions". Molecules 28, nr 7 (24.03.2023): 2916. http://dx.doi.org/10.3390/molecules28072916.

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Recently, we revealed the electronic nature of the tubular Au26 based on spherical aromaticity. The peculiar structure of the Au26 could be an ideal catalyst model for studying the adsorptions of the Au nanotubes. However, through Google Scholar, we found that no one has reported connections between the structure and reactivity properties of Au26. Here, three kinds of molecules are selected to study the fundamental adsorption behaviors that occur on the surface of Au26. When one CO molecule is adsorbed on the Au26, the σ-hole adsorption structure is quickly identified as belonging to a ground state energy, and it still maintains integrity at a temperature of 500 K, where σ donations and π-back donations take place; however, two CO molecules make the structure of Au26 appear with distortions or collapse. When one H2 is adsorbed on the Au26, the H–H bond length is slightly elongated due to charge transfers to the anti-bonding σ* orbital of H2. The Au26-H2 can maintain integrity within 100 fs at 300 K and the H2 molecule starts moving away from the Au26 after 200 fs. Moreover, the Au26 can act as a Lewis base to stabilize the electron-deficient BH3 molecule, and frontier molecular orbitals overlap between the Au26 and BH3.

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40

Harbottle, John, i Nikolay Zenkin. "Ureidothiophene inhibits interaction of bacterial RNA polymerase with –10 promotor element". Nucleic Acids Research 48, nr 14 (11.07.2020): 7914–23. http://dx.doi.org/10.1093/nar/gkaa591.

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Abstract Bacterial RNA polymerase is a potent target for antibiotics, which utilize a plethora of different modes of action, some of which are still not fully understood. Ureidothiophene (Urd) was found in a screen of a library of chemical compounds for ability to inhibit bacterial transcription. The mechanism of Urd action is not known. Here, we show that Urd inhibits transcription at the early stage of closed complex formation by blocking interaction of RNA polymerase with the promoter –10 element, while not affecting interactions with –35 element or steps of transcription after promoter closed complex formation. We show that mutation in the region 1.2 of initiation factor σ decreases sensitivity to Urd. The results suggest that Urd may directly target σ region 1.2, which allosterically controls the recognition of –10 element by σ region 2. Alternatively, Urd may block conformational changes of the holoenzyme required for engagement with –10 promoter element, although by a mechanism distinct from that of antibiotic fidaxomycin (lipiarmycin). The results suggest a new mode of transcription inhibition involving the regulatory domain of σ subunit, and potentially pinpoint a novel target for development of new antibacterials.

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41

Lu, Qiang, Taiyu Chen, Jiening Wang, Feng Wang, Wenlong Ye, Lixin Ma i Shan Wu. "Structural Insight into the Mechanism of σ32-Mediated Transcription Initiation of Bacterial RNA Polymerase". Biomolecules 13, nr 5 (25.04.2023): 738. http://dx.doi.org/10.3390/biom13050738.

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Bacterial RNA polymerases (RNAP) form distinct holoenzymes with different σ factors to initiate diverse gene expression programs. In this study, we report a cryo-EM structure at 2.49 Å of RNA polymerase transcription complex containing a temperature-sensitive bacterial σ factor, σ32 (σ32-RPo). The structure of σ32-RPo reveals key interactions essential for the assembly of E. coli σ32-RNAP holoenzyme and for promoter recognition and unwinding by σ32. Specifically, a weak interaction between σ32 and −35/−10 spacer is mediated by T128 and K130 in σ32. A histidine in σ32, rather than a tryptophan in σ70, acts as a wedge to separate the base pair at the upstream junction of the transcription bubble, highlighting the differential promoter-melting capability of different residue combinations. Structure superimposition revealed relatively different orientations between βFTH and σ4 from other σ-engaged RNAPs and biochemical data suggest that a biased σ4–βFTH configuration may be adopted to modulate binding affinity to promoter so as to orchestrate the recognition and regulation of different promoters. Collectively, these unique structural features advance our understanding of the mechanism of transcription initiation mediated by different σ factors.

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42

Thakur, Krishan Gopal, Ravi Kumar Jaiswal, Jinal K. Shukla, T. Praveena i B. Gopal. "Over-expression and purification strategies for recombinant multi-protein oligomers: A case study of Mycobacterium tuberculosis σ/anti-σ factor protein complexes". Protein Expression and Purification 74, nr 2 (grudzień 2010): 223–30. http://dx.doi.org/10.1016/j.pep.2010.06.018.

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43

Weinhold, Frank. "Anti-Electrostatic Pi-Hole Bonding: How Covalency Conquers Coulombics". Molecules 27, nr 2 (7.01.2022): 377. http://dx.doi.org/10.3390/molecules27020377.

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Intermolecular bonding attraction at π-bonded centers is often described as “electrostatically driven” and given quasi-classical rationalization in terms of a “pi hole” depletion region in the electrostatic potential. However, we demonstrate here that such bonding attraction also occurs between closed-shell ions of like charge, thereby yielding locally stable complexes that sharply violate classical electrostatic expectations. Standard DFT and MP2 computational methods are employed to investigate complexation of simple pi-bonded diatomic anions (BO−, CN−) with simple atomic anions (H−, F−) or with one another. Such “anti-electrostatic” anion–anion attractions are shown to lead to robust metastable binding wells (ranging up to 20–30 kcal/mol at DFT level, or still deeper at dynamically correlated MP2 level) that are shielded by broad predissociation barriers (ranging up to 1.5 Å width) from long-range ionic dissociation. Like-charge attraction at pi-centers thereby provides additional evidence for the dominance of 3-center/4-electron (3c/4e) nD-π*AX interactions that are fully analogous to the nD-σ*AH interactions of H-bonding. Using standard keyword options of natural bond orbital (NBO) analysis, we demonstrate that both n-σ* (sigma hole) and n-π* (pi hole) interactions represent simple variants of the essential resonance-type donor-acceptor (Bürgi–Dunitz-type) attraction that apparently underlies all intermolecular association phenomena of chemical interest. We further demonstrate that “deletion” of such π*-based donor-acceptor interaction obliterates the characteristic Bürgi–Dunitz signatures of pi-hole interactions, thereby establishing the unique cause/effect relationship to short-range covalency (“charge transfer”) rather than envisioned Coulombic properties of unperturbed monomers.

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44

Beaucher, Jocelyn, Sébastien Rodrigue, Pierre-Étienne Jacques, Issar Smith, Ryszard Brzezinski i Luc Gaudreau. "Novel Mycobacterium tuberculosis anti-σ factor antagonists control σF activity by distinct mechanisms". Molecular Microbiology 45, nr 6 (27.09.2002): 1527–40. http://dx.doi.org/10.1046/j.1365-2958.2002.03135.x.

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45

Luebke, Justin L., Daniel S. Eaton, Joseph R. Sachleben i Sean Crosson. "Allosteric control of a bacterial stress response system by an anti-σ factor". Molecular Microbiology 107, nr 2 (8.12.2017): 164–79. http://dx.doi.org/10.1111/mmi.13868.

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Aldridge, Phillip, Joyce E. Karlinsey, Eric Becker, Fabienne F. V. Chevance i Kelly T. Hughes. "Flk prevents premature secretion of the anti-σ factor FlgM into the periplasm". Molecular Microbiology 61, nr 1 (9.05.2006): 269. http://dx.doi.org/10.1111/j.1365-2958.2006.05201.x.

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ROBERTS, H. L. L., L. CHANG i C. D. ROBERTS. "IMPACT OF DYNAMICAL CHIRAL SYMMETRY BREAKING ON MESON STRUCTURE AND INTERACTIONS". International Journal of Modern Physics A 26, nr 03n04 (10.02.2011): 371–77. http://dx.doi.org/10.1142/s0217751x11051688.

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We provide a glimpse of recent progress in meson physics made via QCD's Dyson-Schwinger equations with: a perspective on confinement and dynamical chiral symmetry breaking (DCSB); a précis on the physics of in-hadron condensates; results for the masses of the π, σ, ρ, a1 mesons and their first-radial excitations; and an illustration of the impact of DCSB on the pion form factor.

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48

Park, Soo-Dong, Jung-Won Youn, Young-Joon Kim, Seok-Myung Lee, Younhee Kim i Heung-Shick Lee. "Corynebacterium glutamicum σ E is involved in responses to cell surface stresses and its activity is controlled by the anti-σ factor CseE". Microbiology 154, nr 3 (1.03.2008): 915–23. http://dx.doi.org/10.1099/mic.0.2007/012690-0.

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Deighan, Padraig, Cristina Montero Diez, Mark Leibman, Ann Hochschild i Bryce E. Nickels. "The bacteriophage λ Q antiterminator protein contacts the β-flap domain of RNA polymerase". Proceedings of the National Academy of Sciences 105, nr 40 (1.10.2008): 15305–10. http://dx.doi.org/10.1073/pnas.0805757105.

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The multisubunit RNA polymerase (RNAP) in bacteria consists of a catalytically active core enzyme (α2ββ′ω) complexed with a σ factor that is required for promoter-specific transcription initiation. During early elongation the stability of interactions between σ and core decreases, in part because of the nascent RNA-mediated destabilization of an interaction between region 4 of σ and the flap domain of the β-subunit (β-flap). The nascent RNA-mediated destabilization of the σ region 4/β-flap interaction is required for the bacteriophage λ Q antiterminator protein (λQ) to engage the RNAP holoenzyme. Here, we provide an explanation for this requirement by showing that λQ establishes direct contact with the β-flap during the engagement process, thus competing with σ70 region 4 for access to the β-flap. We also show that λQ's affinity for the β-flap is calibrated to ensure that λQ activity is restricted to the λ late promoter PR′. Specifically, we find that strengthening the λQ/β-flap interaction allows λQ to bypass the requirement for specific cis-acting sequence elements, a λQ-DNA binding site and a RNAP pause-inducing element, that normally ensure λQ is recruited exclusively to transcription complexes associated with PR′. Our findings demonstrate that the β-flap can serve as a direct target for regulators of elongation.

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VIOLA, MARIA GRAZIA. "ON A SUBFACTOR CONSTRUCTION OF A FACTOR NON-ANTIISOMORPHIC TO ITSELF". International Journal of Mathematics 15, nr 08 (październik 2004): 833–54. http://dx.doi.org/10.1142/s0129167x04002570.

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We define a ℤ3-kernel α on [Formula: see text] and a ℤ3-kernel β on the hyperfinite II 1 factor R, which have conjugate obstruction to lifting. Hence, α⊗β can be perturbed by an inner automorphism to produce an action γ on [Formula: see text]. The aim of this paper is to show that the factor [Formula: see text], which is similar to Connes's example of a II 1 factor non-antiisomorphic to itself, is the enveloping algebra of an inclusion of II 1 factors A⊂B. Here A is an interpolated free group factor and B is isomorphic to the crossed product A⋊θℤ9, where θ is a ℤ3-kernel of A with non-trivial obstruction to lifting. By using an argument due to Connes, which involves the invariant χ(ℳ), we show that ℳ is not anti-isomorphic to itself. Furthermore, we prove that for one of the generator of χ(ℳ), which we will denote by σ, the Jones invariant ϰ(σ) is equal to [Formula: see text].

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