[ASAP] A New Class of EutT ATP:Co(I)rrinoid Adenosyltransferases Found in <italic toggle=”yes”>Listeria monocytogenes</italic> and Other <italic toggle=”yes”>Firmicutes</italic> Does Not Require a Metal Ion for Activity

August 15th, 2018 by Flavia G. Costa, Jorge C. Escalante-Semerena

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Biochemistry
DOI: 10.1021/acs.biochem.8b00715

Poxviral protein E3-altered cytokine production reveals that DExD/H-box helicase 9 controls Toll-like receptor-stimulated immune responses [Signal Transduction]

August 15th, 2018 by Alan Dempsey, Sinead E. Keating, Michael Carty, Andrew G. Bowie

Host pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) detect viruses and other pathogens, inducing production of cytokines that cause inflammation and mobilize cells to control infection. Vaccinia virus (VACV) encodes proteins that antagonize these host innate immune responses, and elucidating the mechanisms of action of these viral proteins helped shed light on PRR signalling mechanisms. The VACV virulence factor E3 is one of the most intensely studied VACV proteins and has multiple effects on host cells, many of which cannot be explained by the currently known cellular targets of E3. Here, we report that E3 expression in human monocytes alters TLR2- and TLR8-dependent cytokine induction, and particularly inhibits IL-6. Using MS, we identified DExD/H-box helicase 9 (DHX9) as an E3 target. Although DHX9 has previously been implicated as a PRR for sensing nucleic acid in dendritic cells, we found no role for DHX9 as a nucleic acid-sensing PRR in monocytes. Rather, DHX9 suppression in these cells phenocopied the effects of E3 expression on TLR2- and TLR8-dependent cytokine induction, in that DHX9 was required for all TLR8-dependent cytokines measured, and for TLR2-dependent IL-6. Further, DHX9 also had a cell- and stimulus-independent role in IL-6 promoter induction. DHX9 enhanced nuclear factor kappa B (NFkB)-dependent IL-6 promoter activation, which was directly antagonized by E3. These results indicate new roles for DHX9 in regulating cytokines in innate immunity and reveal that VACV E3 disrupts innate immune responses by targeting of DHX9.
  • Posted in Journal of Biological Chemistry, Publications
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[ASAP] Human Milk Oligosaccharides (HMOs) Sensitize Group B <italic toggle=”yes”>Streptococcus</italic> to Clindamycin, Erythromycin, Gentamicin, and Minocycline on a Strain Specific Basis

August 5th, 2018 by Kelly M. Craft, Jennifer A. Gaddy, Steven D. Townsend

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ACS Chemical Biology
DOI: 10.1021/acschembio.8b00661
  • Posted in ACS Chemical Biology, Publications
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[ASAP] Discovery of a Nitric Oxide Responsive Quorum Sensing Circuit in <italic toggle=”yes”>Vibrio cholerae</italic>

August 2nd, 2018 by Sajjad Hossain, Ilana Heckler, Elizabeth M. Boon

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ACS Chemical Biology
DOI: 10.1021/acschembio.8b00360
  • Posted in ACS Chemical Biology, Publications
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The Saccharomyces cerevisiae Hrq1 and Pif1 DNA helicases synergistically modulate telomerase activity in vitro [Enzymology]

August 1st, 2018 by David G. Nickens, Cody M. Rogers, Matthew L. Bochman

Telomere length homeostasis is vital to maintaining genomic stability and is regulated by multiple factors, including telomerase activity and DNA helicases. The Saccharomyces cerevisiae Pif1 helicase was the first discovered catalytic inhibitor of telomerase, but recent experimental evidence suggests that Hrq1, the yeast homolog of the disease-linked human RecQ-like helicase 4 (RECQL4), plays a similar role via an undefined mechanism. Using yeast extracts enriched for telomerase activity and an in vitro primer extension assay, here we determined the effects of recombinant wild-type and inactive Hrq1 and Pif1 on total telomerase activity and telomerase processivity. We found that titrations of these helicases alone have equal-but-opposite biphasic effects on telomerase, with Hrq1 stimulating activity at high concentrations. When the helicases were combined in reactions, however, they synergistically inhibited or stimulated telomerase activity depending on which helicase was catalytically active. These results suggest that Hrq1 and Pif1 interact and that their concerted activities ensure proper telomere length homeostasis in vivo. We propose a model in which Hrq1 and Pif1 cooperatively contribute to telomere length homeostasis in yeast.

[ASAP] <italic toggle=”yes”>In Vitro</italic> Transcription Networks Based on Hairpin Promoter Switches

July 31st, 2018 by Shaunak Kar, Andrew D. Ellington

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00172
  • Posted in ACS Synthetic Biology, Publications
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Gramibactin is a bacterial siderophore with a diazeniumdiolate ligand system

July 30th, 2018 by Ron Hermenau

Gramibactin is a bacterial siderophore with a diazeniumdiolate ligand system

Gramibactin is a bacterial siderophore with a diazeniumdiolate ligand system, Published online: 30 July 2018; doi:10.1038/s41589-018-0101-9

Plant-associated rhizosphere bacteria produce gramibactin, a cyclic lipodepsipeptide siderophore that tightly binds iron via an unexpected functional group, the N-nitrosohydroxylamine (diazeniumdiolate) moieties of the amino acid graminine.
  • Posted in Nat Chem Biol, Publications
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A multicolor riboswitch-based platform for imaging of RNA in live mammalian cells

July 30th, 2018 by Esther Braselmann

A multicolor riboswitch-based platform for imaging of RNA in live mammalian cells

A multicolor riboswitch-based platform for imaging of RNA in live mammalian cells, Published online: 30 July 2018; doi:10.1038/s41589-018-0103-7

A new riboswitch-based RNA sensor called Riboglow binds to quenched fluorescent probes to induce fluorescence turn-on. Riboglow enables tagging and tracking of mRNA and short noncoding RNAs with different colored fluorophores in live mammalian cells.
  • Posted in Nat Chem Biol, Publications
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Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS

July 30th, 2018 by William H. Zhang

Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS

Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS, Published online: 30 July 2018; doi:10.1038/s41589-018-0108-2

A genetically encoded FRET-based optical sensor generated from a computational design approach can monitor hippocampal glycine levels in brain tissue to determine differences between spines and shafts and changes induced by high- and low-frequency stimulation.
  • Posted in Nat Chem Biol, Publications
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Designed peptides that assemble into cross-α amyloid-like structures

July 30th, 2018 by Shao-Qing Zhang

Designed peptides that assemble into cross-α amyloid-like structures

Designed peptides that assemble into cross-α amyloid-like structures, Published online: 30 July 2018; doi:10.1038/s41589-018-0105-5

Structural analysis reveals how certain designed peptides adopt unusual spiraling cross-α amyloid-like structures and also rearrange to helical polymers upon mutation of small nonpolar residues that are critical for packing and stabilization.
  • Posted in Nat Chem Biol, Publications
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