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
  • Comments Off on Allosteric substrate switching in a voltage-sensing lipid phosphatase

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
  • Comments Off on 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]

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

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.5b01163

Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome

February 10th, 2016 by Xiaoyu Li

Nature Chemical Biology 12, 311 (2016). doi:10.1038/nchembio.2040

Authors: Xiaoyu Li, Xushen Xiong, Kun Wang, Lixia Wang, Xiaoting Shu, Shiqing Ma & Chengqi Yi

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome

Engineering nonphosphorylative metabolism to generate lignocellulose-derived products

February 8th, 2016 by Yi-Shu Tai

Nature Chemical Biology 12, 247 (2016). doi:10.1038/nchembio.2020

Authors: Yi-Shu Tai, Mingyong Xiong, Pooja Jambunathan, Jingyu Wang, Jilong Wang, Cole Stapleton & Kechun Zhang

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Engineering nonphosphorylative metabolism to generate lignocellulose-derived products

A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2

February 8th, 2016 by Jessika Valero-González

Nature Chemical Biology 12, 240 (2016). doi:10.1038/nchembio.2019

Authors: Jessika Valero-González, Christina Leonhard-Melief, Erandi Lira-Navarrete, Gonzalo Jiménez-Osés, Cristina Hernández-Ruiz, María Carmen Pallarés, Inmaculada Yruela, Deepika Vasudevan, Anabel Lostao, Francisco Corzana, Hideyuki Takeuchi, Robert S Haltiwanger & Ramon Hurtado-Guerrero

  • Posted in Nat Chem Biol, Publications
  • Comments Off on A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2

A transcription activator–like effector (TALE) induction system mediated by proteolysis

February 8th, 2016 by Matthew F Copeland

Nature Chemical Biology 12, 254 (2016). doi:10.1038/nchembio.2021

Authors: Matthew F Copeland, Mark C Politz, Charles B Johnson, Andrew L Markley & Brian F Pfleger

  • Posted in Nat Chem Biol, Publications
  • Comments Off on A transcription activator–like effector (TALE) induction system mediated by proteolysis

Design principles involving protein disorder facilitate specific substrate selection and degradation by the ubiquitin-proteasome system [Protein Synthesis and Degradation]

February 5th, 2016 by Guharoy, M., Bhowmick, P., Tompa, P.

The ubiquitin-proteasome system (UPS) regulates diverse cellular pathways by the timely removal (or processing) of proteins. Here we review the role of structural disorder and conformational flexibility in the different aspects of degradation. First, we discuss posttranslational modifications within disordered regions that regulate E3 ligase localization, conformation and enzymatic activity, and also the role of flexible linkers in mediating ubiquitin transfer and reaction processivity. Next we review well-studied substrates and discuss that substrate elements (degrons) recognized by E3 ligases are highly disordered: short linear motifs recognized by many E3s constitute an important class of degrons and these are almost always present in disordered regions. Substrate lysines targeted for ubiquitination are also often located in neighboring regions of the E3 docking motifs and are therefore part of the disordered segment. Finally, biochemical experiments and predictions show that initiation of degradation at the 26S proteasome requires a partially unfolded region to facilitate substrate entry into the proteasomal core.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on Design principles involving protein disorder facilitate specific substrate selection and degradation by the ubiquitin-proteasome system [Protein Synthesis and Degradation]