Nature Chemical Biology Contents: March 2015, Volume 11 No 3 pp 174 - 235

TABLE OF CONTENTS March 2015 Volume 11, Issue 3 Research Highlights News and Views Perspective Brief Communications Articles Errata Corrigendum Subscribe Facebook RSS Recommend to library Twitter Advertisement Featured contents published recently in Experimental & Molecular Medicine (EMM): Special Feature on Stem Cells: Current Research and Future Prospects Special Feature on Mucosal Immunity and Vaccines  EMM publishes the latest and most important advances in genetic, molecular and cellular studies of human physiology and diseases. Register for your Electronic Table of Contents e-alerts today!  RESEARCH HIGHLIGHTS Quorum sensing: mRNA tug of war | Non-natural amino acids: A synthetase swap |Protein aggregation: Curling damage | Protein design: We built this protein | RNA epigenetics: m6A partial differential | Lipid-protein interactions: Three sites in PTEN NEWS AND VIEWS Protein aggregation: Close encounters of the greasy kind   pp176 - 177 Daniel Otzen doi:10.1038/nchembio.1759 Aggregation of α-synuclein (αSN) is critical to the development of Parkinson's disease (PD), but the role of membranes in this process has been unclear and controversial. Galvagnion et al. demonstrate and model how lipids can stimulate αSN aggregation over a narrow range of lipid:protein stoichiometries. See also: Article by Galvagnion et al. Natural products: Untwisting the antibiotic'ome   pp177 - 178 Chad W Johnston and Nathan A Magarvey doi:10.1038/nchembio.1757 Microbial natural products and the specific subset with antibiotic activity, 'the antibiotic'ome', consist of a dizzying array of structures and exert their effects by many known modes of action. In this issue, Cociancich et al. describe a unique natural product that—along with a compound identified in a recent publication by Baumann et al.—defines a new antibacterial chemical scaffold that acts on a rarely hit target, DNA gyrase subunit A. See also: Brief Communication by Cociancich et al. Stress response: PARP1 911   pp179 - 180 Florian J Bock and Paul Chang doi:10.1038/nchembio.1756 Although resveratrol is thought to provide many beneficial health effects, its cellular targets and mechanism of function are still under investigation. A new study found that resveratrol binds to tyrosyl transfer-RNA synthetase, resulting in the activation of the stress response effector PARP1. Metabolism: 'Channeling' Hans Krebs   pp180 - 181 Danielle Tullman-Ercek doi:10.1038/nchembio.1758 The physical arrangement of enzymes within native metabolic pathways is emerging as an important but underexplored area of molecular biology. Recent advances in mass spectrometry enabled confirmation of the proposal that the Krebs cycle enzymes form a complex and suggest that substrate channeling is the most likely benefit to this structural arrangement. Chemical Biology  JOBS of the week Project leader Karolinska Institutet (KI) Research Fellow Position in Nanomedicine Nanyang Technological University (NTU) Senior research associate in nanotechnology for biodetection Houston Methodist Research Institute More Science jobs from Chemical Biology EVENT The Expanding Toolbox of Medicinal Chemistry: From Chemical Biology to Clinical Applications  16 October 2015 Dijon, France More science events from PERSPECTIVE Collective antibiotic tolerance: mechanisms, dynamics and intervention   pp182 - 188 Hannah R Meredith, Jaydeep K Srimani, Anna J Lee, Allison J Lopatkin and Lingchong You doi:10.1038/nchembio.1754 This Perspective describes the different modes by which bacteria belonging to a population can achieve resistance to antibiotic treatments that are otherwise lethal to individual cells and suggests that such mechanisms of collective antibiotic tolerance can be targeted for development of antimicrobials. BRIEF COMMUNICATIONS Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation   pp189 - 191 Huw D Lewis, John Liddle, Jim E Coote, Stephen J Atkinson, Michael D Barker et al. doi:10.1038/nchembio.1735 Inhibitors of the PAD4 enzyme that bind the inactive enzyme link this protein deiminase and the resultant arginine-to-citrulline modification to formation of neutrophil extracellular traps, highly decondensed chromatin structures with both host-defense and pathological roles. Chemical compounds Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases   pp192 - 194 Jannik Bruun Larsen, Martin Borch Jensen, Vikram K Bhatia, Søren L Pedersen, Thomas Bjørnholm et al. doi:10.1038/nchembio.1733 Membrane sorting of Ras and its isolated lipid anchor is based on membrane curvature, sensed by Ras itself. This helps to explain the previous inability to match in vivoresults in vitro in promoting the raftophilic Ras to partition with membrane lipid rafts. The gyrase inhibitor albicidin consists of p-aminobenzoic acids and cyanoalanine   pp195 - 197 Stéphane Cociancich, Alexander Pesic, Daniel Petras, Stefanie Uhlmann, Julian Kretz et al. doi:10.1038/nchembio.1734 The natural product albicidin is known to be a potential antibacterial agent, but its missing structure has stymied further studies. Structural determination and biochemical tests of NRPS domains now identify an unusual p-aminobenzoic acid–based compound. Chemical compounds See also: News and Views by Johnston & Magarvey A light-inducible CRISPR-Cas9 system for control of endogenous gene activation   pp198 - 200 Lauren R Polstein and Charles A Gersbach doi:10.1038/nchembio.1753 Modification of the CRISPR/Cas9 genome editing system by the addition of the light inducible proteins CRY2 and CIBI1 enables blue light–mediated transcription of endogenous genes in mammalian cells. ARTICLES Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine   pp201 - 206 Ohad Iosefson, Andrew R Nager, Tania A Baker and Robert T Sauer doi:10.1038/nchembio.1732 The construction of ClpX hexamers containing variable numbers and configurations of wild-type and grip-defective pore loops supports a model of concurrent loop movement that ensures substrate unfolding and translocation. Modular construction of mammalian gene circuits using TALE transcriptional repressors   pp207 - 213 Yinqing Li, Yun Jiang, He Chen, Weixi Liao, Zhihua Li et al. doi:10.1038/nchembio.1736 Reversible transcriptional repressors are built with TALE proteins on the basis of steric hindrance of a new promoter architecture in an RNA-sensitive manner, enabling applications in mammalian cells such as classification of cancerous versus noncancerous cells. Creating small transcription activating RNAs   pp214 - 220 James Chappell, Melissa K Takahashi and Julius B Lucks doi:10.1038/nchembio.1737 RNA has been used in a variety of synthetic biology circuits but never as a transcriptional activator. Two design strategies using synthetic and natural sequences now lead to RNA activators, enabling RNA-only logic gates. Local and macroscopic electrostatic interactions in single α-helices   pp221 - 228 Emily G Baker, Gail J Bartlett, Matthew P Crump, Richard B Sessions, Noah Linden et al. doi:10.1038/nchembio.1739 A series of designed peptides call the sphere of influence of the helix macrodipole into question, showing that the favorable rotamers allowed by K→E hydrogen bonds beat out the entropically penalized but macrodipole-aligned E→K hydrogen bonds. Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation   pp229 - 234 Céline Galvagnion, Alexander K Buell, Georg Meisl, Thomas C T Michaels, Michele Vendruscolo et al. doi:10.1038/nchembio.1750 Small unilamellar vesicles composed of the negatively charged lipid DMPS enhance the aggregation of the Lewy Body disease protein α-synuclein by increasing the rate of primary nucleation by a thousandfold. See also: News and Views by Otzen ERRATA Erratum: Rick Morimoto   p235 Catherine Goodman doi:10.1038/nchembio0315-235a Erratum: Covalent docking of large libraries for the discovery of chemical probes   p235 Nir London, Rand M Miller, Shyam Krishnan, Kenji Uchida, John J Irwin et al. doi:10.1038/nchembio0315-235b Subcellular metal imaging identifies dynamic sites of Cu accumulation inChlamydomonas   p235 Anne Hong-Hermesdorf, Marcus Miethke, Sean D Gallaher, Janette Kropat, Sheel C Dodani et al. doi:10.1038/nchembio0315-235c CORRIGENDUM Corrigendum: Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs   p235 Lingyin Li, Qian Yin, Pia Kuss, Zoltan Maliga, Jose L Millan et al. doi:10.1038/nchembio0315-235d Advertisement Don't let your data go to waste...  Scientific Data helps researchers make the most of their data, offering publication in a peer reviewed open access journal. We welcome data of all sizes, from all areas of science. What's unique? 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