Translation: Ribosomes make sweeping arrests

February 16th, 2016 by Diego A Alonzo

Nature Chemical Biology 12, 127 (2016). doi:10.1038/nchembio.2027

Authors: Diego A Alonzo & T Martin Schmeing

The arrest peptides that function with the macrolide antibiotic erythromycin stall translating ribosomes in the presence of the antibiotic, leading to remodeling of the downstream mRNA and enhancement of the translation of resistance genes. Current work suggests that small changes in the nascent peptide dictate the ability of ribosomes to respond to this and other small molecules.

Target identification: Getting cholesterol out

February 16th, 2016 by Mirella Bucci

Nature Chemical Biology 12, 125 (2016). doi:10.1038/nchembio.2032

Author: Mirella Bucci

RNA modification: Translating for growth

February 16th, 2016 by Grant Miura

Nature Chemical Biology 12, 125 (2016). doi:10.1038/nchembio.2034

Author: Grant Miura

Molecular Modeling of the Structural and Dynamical Changes in Calcium Channel TRPV5 Induced by the African-Specific A563T Variation

February 15th, 2016 by Lingyun Wang, Ross P. Holmes and Ji-Bin Peng

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DOI: 10.1021/acs.biochem.5b00732

YihQ is a sulfoquinovosidase that cleaves sulfoquinovosyl diacylglyceride sulfolipids

February 15th, 2016 by Gaetano Speciale

Nature Chemical Biology 12, 215 (2016). doi:10.1038/nchembio.2023

Authors: Gaetano Speciale, Yi Jin, Gideon J Davies, Spencer J Williams & Ethan D Goddard-Borger

Sulfoquinovose is produced by photosynthetic organisms at a rate of 1010 tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studies unveiled the sequence signatures for binding the distinguishing sulfonate residue and revealed that sulfoquinovoside degradation is widespread across the tree of life.

  • Posted in Nat Chem Biol, Publications
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Allostery: A lipid two-step

February 15th, 2016 by Liang Hong

Nature Chemical Biology 12, 202 (2016). doi:10.1038/nchembio.2037

Authors: Liang Hong & Francesco Tombola

A sensor of membrane depolarization controls the activity of a bound enzyme through a novel mechanism involving two sequential voltage-dependent transitions allosterically coupled to changes in the substrate specificity of the catalytic domain.

Allosteric substrate switching in a voltage-sensing lipid phosphatase

February 15th, 2016 by Sasha S Grimm

Nature Chemical Biology 12, 261 (2016). doi:10.1038/nchembio.2022

Authors: Sasha S Grimm & Ehud Y Isacoff

  • Posted in Nat Chem Biol, Publications
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Transcription elongation factor NusA is a general antagonist of Rho-dependent termination in Escherichia coli. [Microbiology]

February 12th, 2016 by Qayyum, M. Z., Dey, D., Sen, R.

NusA is an essential protein that binds to RNA polymerase (RNAP) and also to the nascent RNA, and influences transcription by inducing pausing and facilitating the process of transcription termination / antitermination. Its participation in Rho-dependent transcription termination has been perceived, but the molecular nature of this involvement is not known. We hypothesized that as both Rho and NusA are RNA-binding proteins and have the potential to target the same RNA, the latter is likely to influence the global pattern of the Rho-dependent termination. Analyses of the nascent RNA-binding properties and consequent effects on the Rho-dependent termination functions of specific NusA-RNA binding domain mutants revealed an existence of Rho-NusA direct competition for the overlapping nut (NusA-binding site) and rut (Rho-binding site) sites on the RNA. This leads to delayed entry of Rho at the rut site that inhibits the RNA release process of the latter. High density tiling micro-array profiles of these NusA mutants revealed that a significant number of genes, together with transcripts from intergenic regions are up-regulated. Interestingly, majority of these genes were also up-regulated when the Rho function was compromised. These are strong evidences for the existence of NusA-binding sites in different operons which are also the targets of Rho-dependent terminations. Our data strongly argue in favor of a direct competition between NusA and Rho for the access of specific sites on the nascent transcripts in different parts of the genome. We propose that this competition enables NusA to function as a global antagonist of the Rho function, which is unlike its role as a facilitator of hairpin-dependent termination.

Regulation of Monocarboxylic Acid Transporter 1 Trafficking by the Canonical Wnt/{beta}-catenin Pathway in Rat Brain Endothelial Cells, Requiring a Crosstalk with Notch Signaling [Signal Transduction]

February 12th, 2016 by Liu, Z., Sneve, M., Haroldson, T. A., Smith, J. P., Drewes, L. R.

The transport of monocarboxylate fuels, such as lactate, pyruvate and ketone bodies, across brain endothelial cells is mediated by monocarboxylic acid transporter 1 (MCT1). Although the canonical Wnt/β-catenin pathway is required for rodent blood-brain barrier (BBB) development and for the expression of associated nutrient transporters, the role of this pathway in regulation of brain endothelial MCT1 is unknown. Here, we report expression of nine members of the frizzled receptor family by the RBE4 rat brain endothelial cell line. Furthermore, activation of the canonical Wnt/β-catenin pathway in RBE4 cells via nuclear β-catenin signaling with lithium chloride (LiCl) does not alter brain endothelial Mct1 mRNA, but increases the amount of MCT1 transporter protein. Plasma membrane biotinylation studies and confocal microscopic examination of mCherry-tagged MCT1 indicate that increased transporter results from reduced MCT1 trafficking from the plasma membrane via the endosomal/lysosomal pathway and is facilitated by decreased MCT1 ubiquitination following LiCl treatment. Inhibition of the Notch pathway by the γ-secretase inhibitor, DAPT, negated the upregulation of MCT1 by LiCl, thus demonstrating a crosstalk between the canonical Wnt/β-catenin and Notch pathways. Our results are important because they show for the first time the regulation of MCT1 in cerebrovascular endothelial cells by the multi-functional canonical Wnt/β-catenin and Notch signaling pathways.
  • Posted in Journal of Biological Chemistry, Publications
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HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid

February 11th, 2016 by Ajit Roy and Akash Ranjan

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DOI: 10.1021/acs.biochem.5b01163