Compartmentalizing acid stress in bacteria

Posted on Oct 15th, 2018 - By Colin Kleanthous

Compartmentalizing acid stress in bacteriaCompartmentalizing acid stress in bacteria, Published online: 15 October 2018; doi:10.1038/s41589-018-0148-7A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific…

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In vivo chloride concentrations surge to proteotoxic levels during acid stress

Posted on Oct 15th, 2018 - By Frederick Stull

In vivo chloride concentrations surge to proteotoxic levels during acid stressIn vivo chloride concentrations surge to proteotoxic levels during acid stress, Published online: 15 October 2018; doi:10.1038/s41589-018-0143-zProtonation of periplasmic protein carboxylic groups creates a Donnan equilibrium in the bacterial periplasmic space at low pH, leading to accumulation of Cl− and unfolding and aggregation of periplasmic proteins, which can be rescued by…

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The splice is right

Posted on Oct 15th, 2018 - By James Palacino

The splice is rightThe splice is right, Published online: 15 October 2018; doi:10.1038/s41589-018-0147-8Current drug discovery efforts focus on proteins because of their ability to form stable, structured pockets. A recent study demonstrates that targeting stable, structured bioactive RNA motifs, such as autocatalytic introns, may provide a novel method of expanding druggability and…

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Small molecules that target group II introns are potent antifungal agents

Posted on Oct 15th, 2018 - By Olga Fedorova

Small molecules that target group II introns are potent antifungal agentsSmall molecules that target group II introns are potent antifungal agents, Published online: 15 October 2018; doi:10.1038/s41589-018-0142-0High-throughput screening followed by an examination of structure–activity relationship-based optimization resulted in the identification of potent small-molecule inhibitors of group IIB intron splicing in fungal…

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New tricks for an old drug

Posted on Oct 8th, 2018 - By Barbara S. Nelson

New tricks for an old drugNew tricks for an old drug, Published online: 08 October 2018; doi:10.1038/s41589-018-0137-xThe prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia…

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MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG

Posted on Oct 8th, 2018 - By Louise Fets

MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOGMCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG, Published online: 08 October 2018; doi:10.1038/s41589-018-0136-yHigh intracellular concentrations of the α-ketoglutarate analog N-oxalylglycine, owing to MCT2-mediated transport of its newly described prodrug MOG, inhibit multiple enzymes in glutamine metabolism and selectively kill MCT2-expressing cancer…

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The substrate lends a hand

Posted on Sep 17th, 2018 - By Albert A. Bowers

The substrate lends a hand The substrate lends a hand, Published online: 17 September 2018; doi:10.1038/s41589-018-0135-zDuramycin is a small post-translationally modified peptide with antibody-like affinity for phosphatidylethanolamine. As it turns out, the same functionality that is essential for duramycin activity helps to catalyze the formation of its conformationally constrained and compact polycyclic…

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Fatal chemoattraction

Posted on Sep 17th, 2018 - By Mirella Bucci

Fatal chemoattractionFatal chemoattraction, Published online: 17 September 2018; doi:10.1038/s41589-018-0140-2Fatal…

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Flipping out the peptide

Posted on Sep 17th, 2018 - By Stephanie Gras

Flipping out the peptideFlipping out the peptide, Published online: 17 September 2018; doi:10.1038/s41589-018-0133-1T cell cross-reactivity enables the immune system to recognize a large array of peptides. A new study shows that T cells can achieve cross-recognition by using the remarkable plasticity of peptides, through flipping the peptide out of the binding…

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Diversifying bases

Posted on Sep 17th, 2018 - By Yiyun Song

Diversifying basesDiversifying bases, Published online: 17 September 2018; doi:10.1038/s41589-018-0141-1Diversifying…

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A new target for thalidomide

Posted on Sep 17th, 2018 - By Peter G. Wells

A new target for thalidomideA new target for thalidomide, Published online: 17 September 2018; doi:10.1038/s41589-018-0134-0One mechanism of thalidomide teratogenicity involves binding to the CUL4–CRBN E3 ubiquitin ligase complex, which then mediates the degradation of transcription factors. New studies reveal that species-specific variants of the transcription factor SALL4 are differentially ubiquitinated and degraded via the thalidomide-bound…

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Cost–benefit analysis

Posted on Sep 17th, 2018 - By Grant Miura

Cost–benefit analysisCost–benefit analysis, Published online: 17 September 2018; doi:10.1038/s41589-018-0139-8Cost–benefit…

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T cell receptor cross-reactivity expanded by dramatic peptide–MHC adaptability

Posted on Sep 17th, 2018 - By Timothy P. Riley

T cell receptor cross-reactivity expanded by dramatic peptide–MHC adaptabilityT cell receptor cross-reactivity expanded by dramatic peptide–MHC adaptability, Published online: 17 September 2018; doi:10.1038/s41589-018-0130-4Structural analysis shows that cross-reactivity of the T cell receptor DMF5 is governed by adaptability of the peptide antigen, which can undergo TCR-binding-induced frameshifting forcing the peptide C terminus to extend from the MHC-binding…

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Post-translational site-selective protein backbone α-deuteration

Posted on Sep 17th, 2018 - By Sébastien R. G. Galan

Post-translational site-selective protein backbone α-deuterationPost-translational site-selective protein backbone α-deuteration, Published online: 17 September 2018; doi:10.1038/s41589-018-0128-yA chemical method for site-selective deuterium exchange at protein backbone α-carbons, involving conversion of cysteine to dehydroalanine and then to deuterated cysteine, is used to explore the mechanism of a model protein bioconjugation…

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SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate

Posted on Sep 6th, 2018 - By Mary E. Matyskiela

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrateSALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate, Published online: 06 September 2018; doi:10.1038/s41589-018-0129-xThalidomide-induced degradation of the transcription factor SALL4 in a cereblon-dependent manner provides an explanation for the teratogenic…

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Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit

Posted on Sep 3rd, 2018 - By Ravikrishna Ramanujam

Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuitEstablishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit, Published online: 03 September 2018; doi:10.1038/s41589-018-0117-1The asymmetric cortical gradient of PAR-1 is patterned via an integration of its cortical exclusion and stabilization by a circuit consisting of aPKC and the PRBH protein…

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Substrate-assisted enzymatic formation of lysinoalanine in duramycin

Posted on Sep 3rd, 2018 - By Linna An

Substrate-assisted enzymatic formation of lysinoalanine in duramycinSubstrate-assisted enzymatic formation of lysinoalanine in duramycin, Published online: 03 September 2018; doi:10.1038/s41589-018-0122-4During the biosynthesis of the lanthipeptide duramycin, DurN catalyzes stereospecific lysinoalanine formation by preorganizing the reactive conformation of the substrate, such that one of the substrate’s own residues serves as the catalytic…

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Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

Posted on Sep 3rd, 2018 - By Salma Akter

Chemical proteomics reveals new targets of cysteine sulfinic acid reductaseChemical proteomics reveals new targets of cysteine sulfinic acid reductase, Published online: 03 September 2018; doi:10.1038/s41589-018-0116-2An electrophilic diazene probe (DiaAlk) enables capture and proteomic analysis of cysteine S-sulfinylation modifications, thus illuminating dynamic responses to oxidative stress and enabling the identification of new substrates of…

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Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3

Posted on Aug 27th, 2018 - By Yuan Fu

Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3, Published online: 27 August 2018; doi:10.1038/s41589-018-0113-5The large subunit of ribonucleotide reductase RNR-α downregulates DNA replication in the nucleus by directly disrupting PCNA and ZRANB3 interactions. RNR-α nuclear entry is regulated by an interplay between IRBIT and…

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Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis

Posted on Aug 27th, 2018 - By Takaaki Taniguchi

Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesisAcetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis, Published online: 27 August 2018; doi:10.1038/s41589-018-0119-zA comparative genomic approach identified a novel acetate-dependent tRNA-modifying enzyme that catalyzes RNA acetylation with a mechanism similar to tRNA aminoacylation. This modification maintains decoding fidelity in protein…

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<i>O</i>-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response

Posted on Aug 20th, 2018 - By Xingqian Zhang

O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response<i>O</i>-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response, Published online: 20 August 2018; doi:10.1038/s41589-018-0120-6O-GlcNAcylation of translation initiation factor component eIF4GI blocks interactions to poly(A)-binding protein Pab1 to induce disassembly of stress granules, releasing Hsp70-induced mRNAs and leading to translation of protective…

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Continuous directed evolution of proteins with improved soluble expression

Posted on Aug 20th, 2018 - By Tina Wang

Continuous directed evolution of proteins with improved soluble expressionContinuous directed evolution of proteins with improved soluble expression, Published online: 20 August 2018; doi:10.1038/s41589-018-0121-5Through use of a split-intein pIII, soluble expression phage-assisted continuous evolution (SE-PACE) enables two simultaneous positive selections to rapidly evolve proteins with improved expression while maintaining their desired…

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Catch and identify your prey

Posted on Aug 17th, 2018 - By Karin Kuehnel

Catch and identify your preyCatch and identify your prey, Published online: 17 August 2018; doi:10.1038/s41589-018-0125-1Catch and identify your…

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A ribonucleotide trap

Posted on Aug 17th, 2018 - By Yiyun Song

A ribonucleotide trapA ribonucleotide trap, Published online: 17 August 2018; doi:10.1038/s41589-018-0127-zA ribonucleotide…

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<i>ykkC</i> riboswitches employ an add-on helix to adjust specificity for polyanionic ligands

Posted on Aug 17th, 2018 - By Alla Peselis

ykkC riboswitches employ an add-on helix to adjust specificity for polyanionic ligands<i>ykkC</i> riboswitches employ an add-on helix to adjust specificity for polyanionic ligands, Published online: 17 August 2018; doi:10.1038/s41589-018-0114-4Structural analysis of PRPP and ppGpp riboswitches reveals that they employ a helical element to create a tunnel for the ligand, whose specificity is determined by the conserved nucleotides forming the tunnel and long-distance…

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TA gets a PG rating

Posted on Aug 17th, 2018 - By Mirella Bucci

TA gets a PG ratingTA gets a PG rating, Published online: 17 August 2018; doi:10.1038/s41589-018-0126-0TA gets a PG…

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Stuck on you

Posted on Aug 17th, 2018 - By Caitlin Deane

Stuck on youStuck on you, Published online: 17 August 2018; doi:10.1038/s41589-018-0124-2Stuck on…

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Mimicking cross-α amyloids

Posted on Aug 17th, 2018 - By Meytal Landau

Mimicking cross-α amyloidsMimicking cross-α amyloids, Published online: 17 August 2018; doi:10.1038/s41589-018-0118-0The design of spiraling cross-α amyloid-like structures reveals fascinating supermolecular fibrils of diverse compactness and stability. The small sequence variations governing cross-α self-assembly properties concur with amyloids being basic building blocks of life and natural targets for microbial structural…

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Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestin

Posted on Aug 17th, 2018 - By Fan Yang

Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestinAllosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestin, Published online: 17 August 2018; doi:10.1038/s41589-018-0115-3NMR and in vitro reconstitution indicate that GPCRs signal through SH3-containing proteins downstream of β-arrestin 1 proline regions and that arrestin allosterically activates downstream kinases by disrupting their autoinhibitory…

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An optical sensor to monitor dynamics of extracellular glycine

Posted on Aug 17th, 2018 - By Dmitri A. Rusakov

An optical sensor to monitor dynamics of extracellular glycineAn optical sensor to monitor dynamics of extracellular glycine, Published online: 17 August 2018; doi:10.1038/s41589-018-0123-3A computational design approach was used to develop a genetically encoded FRET-based optical sensor that is aimed at monitoring extracellular glycine levels in brain tissue with the sensitivity and resolution to discern differences in dendritic spine and shaft environment and concentration dynamics upon…

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Gramibactin is a bacterial siderophore with a diazeniumdiolate ligand system

Posted on Jul 30th, 2018 - By Ron Hermenau

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

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

Posted on Jul 30th, 2018 - By Shao-Qing Zhang

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

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Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS

Posted on Jul 30th, 2018 - By William H. Zhang

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

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

Posted on Jul 30th, 2018 - By Esther Braselmann

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

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Dopamine gets lit

Posted on Jul 17th, 2018 - By Mirella Bucci

Dopamine gets litDopamine gets lit, Published online: 17 July 2018; doi:10.1038/s41589-018-0111-7Dopamine gets…

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A remote control for switching

Posted on Jul 17th, 2018 - By Marc Vendrell

A remote control for switchingA remote control for switching, Published online: 17 July 2018; doi:10.1038/s41589-018-0107-3Calcium channels are crucial regulators of a broad range of biological processes. A photoswitchable chemical probe allows the opening and closing of these channels with unprecedented temporal resolution, providing new opportunities to study calcium-dependent signaling pathways in real…

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Crowd control

Posted on Jul 17th, 2018 - By Grant Miura

Crowd controlCrowd control, Published online: 17 July 2018; doi:10.1038/s41589-018-0109-1Crowd…

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3D interaction hubs

Posted on Jul 17th, 2018 - By Yiyun Song

3D interaction hubs3D interaction hubs, Published online: 17 July 2018; doi:10.1038/s41589-018-0112-63D interaction…

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Antigen processing movers and shakers

Posted on Jul 17th, 2018 - By Tim Elliott

Antigen processing movers and shakersAntigen processing movers and shakers, Published online: 17 July 2018; doi:10.1038/s41589-018-0106-4Monitoring MHC-I dynamics upon binding to its chaperone TAPBPR helps us understand how optimal peptide sequences are selected for presentation and coordinated with release of the chaperone from the ternary peptide–MHC-I–TAPBPR…

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Caught in the act

Posted on Jul 17th, 2018 - By Karin Kuehnel

Caught in the actCaught in the act, Published online: 17 July 2018; doi:10.1038/s41589-018-0110-8Caught in the…

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Facile target validation in an animal model with intracellularly expressed monobodies

Posted on Jul 16th, 2018 - By Ankit Gupta

Facile target validation in an animal model with intracellularly expressed monobodiesFacile target validation in an animal model with intracellularly expressed monobodies, Published online: 16 July 2018; doi:10.1038/s41589-018-0099-zThe development of a selective and potent monobody to WDR5, a component of the mixed linear leukemia methyltransferase complex, as genetically encoded inhibitor enables suppression of leukemogenesis and confers survival in a mouse leukemia…

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Acetylation blocks DNA damage–induced chromatin ADP-ribosylation

Posted on Jul 16th, 2018 - By Glen Liszczak

Acetylation blocks DNA damage–induced chromatin ADP-ribosylationAcetylation blocks DNA damage–induced chromatin ADP-ribosylation, Published online: 16 July 2018; doi:10.1038/s41589-018-0097-1Histone H3 serine 10 is found to be the major chromatin acceptor residue for DNA damage–induced ADP-ribosylation and is blocked by specific acetylation sites on PARP1 and/or…

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PAINTing translation

Posted on Jul 9th, 2018 - By Yuichiro Mishima

PAINTing translationPAINTing translation, Published online: 09 July 2018; doi:10.1038/s41589-018-0102-8Establishment of the germ cell lineage requires post-transcriptional regulation of mRNAs, yet the underlying molecular mechanisms are not fully understood in vertebrates. A small-molecule inhibitor of germ cell formation reveals a noncanonical translation system used in zebrafish…

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Noncanonical translation via deadenylated 3′ UTRs maintains primordial germ cells

Posted on Jul 9th, 2018 - By Youngnam N. Jin

Noncanonical translation via deadenylated 3′ UTRs maintains primordial germ cellsNoncanonical translation via deadenylated 3′ UTRs maintains primordial germ cells, Published online: 09 July 2018; doi:10.1038/s41589-018-0098-0Primordazine inhibits poly(A)-tail-independent noncanonical translation (PAINT) in early zebrafish embryos and in mammalian cells under select conditions, an effect mediated by deadenylated 3ʹ UTRs that results in ablation of primordial germ…

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Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle

Posted on Jul 9th, 2018 - By Andrew C. McShan

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cyclePeptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle, Published online: 09 July 2018; doi:10.1038/s41589-018-0096-2Use of NMR to monitor MHC-I dynamics upon binding to the MHC-I chaperone TAPBPR explains the selection of optimal peptide sequences and release of the chaperone from the ternary peptide-MHC-I–TAPBPR…

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Publisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases

Posted on Jun 27th, 2018 - By Suzana Markolovic

Publisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPasesPublisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases, Published online: 27 June 2018; doi:10.1038/s41589-018-0104-6Publisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC…

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Designing microbial consortia with defined social interactions

Posted on Jun 25th, 2018 - By Wentao Kong

Designing microbial consortia with defined social interactionsDesigning microbial consortia with defined social interactions, Published online: 25 June 2018; doi:10.1038/s41589-018-0091-7Synthetic microbial consortia were engineered as experimental models of bacterial interactions within ecosystems, and mathematical models of their behavior were used to design more complex microbial systems with additional…

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Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization modes

Posted on Jun 25th, 2018 - By Thu-Thuy T. Dang

Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization modesSarpagan bridge enzyme has substrate-controlled cyclization and aromatization modes, Published online: 25 June 2018; doi:10.1038/s41589-018-0078-4Three homologous cytochrome P450s from monoterpene indole alkaloid-producing plants enable the identification of sarpagan bridge enzyme, which catalyzes either cyclization or aromatization to yield sarpagan or β-carboline alkaloids,…

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Metabolic engineering of a carbapenem antibiotic synthesis pathway in <i>Escherichia coli</i>

Posted on Jun 25th, 2018 - By Helena Shomar

Metabolic engineering of a carbapenem antibiotic synthesis pathway in Escherichia coliMetabolic engineering of a carbapenem antibiotic synthesis pathway in <i>Escherichia coli</i>, Published online: 25 June 2018; doi:10.1038/s41589-018-0084-6Efficient production of a simple carbapenem antibiotic in Escherichia coli is achieved by a combination of feedback-resistant enzymes for increased precursor biosynthesis and inhibition of fatty acid synthesis for tolerance toward the toxic…

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Cleavage of a carbon–fluorine bond by an engineered cysteine dioxygenase

Posted on Jun 25th, 2018 - By Jiasong Li

Cleavage of a carbon–fluorine bond by an engineered cysteine dioxygenaseCleavage of a carbon–fluorine bond by an engineered cysteine dioxygenase, Published online: 25 June 2018; doi:10.1038/s41589-018-0085-5Engineered variants of cysteine dioxygenase containing a halogen-substituted tyrosine analog provide insights into the process of Cys–Tyr cross-link formation and indicate that the enzyme can catalyze oxidative cleavage of a carbon–fluorine…

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Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer

Posted on Jun 25th, 2018 - By Hayley J. Donnella

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancerKinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer, Published online: 25 June 2018; doi:10.1038/s41589-018-0081-9Proteomic mapping of dynamic changes in kinase signaling after drug treatment identifies that AURKA inhibition is required for drug sensitivity, representing a new co-targeting opportunity with PI3K, AKT, or mTOR inhibitors in breast…

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Unraveling the rewired network

Posted on Jun 25th, 2018 - By Vinayak Palve

Unraveling the rewired networkUnraveling the rewired network, Published online: 25 June 2018; doi:10.1038/s41589-018-0083-7Adaptive survival signaling can promote resistance to individual kinase inhibitors. A new study used a pathway-based approach to characterize shared kinome-wide rewiring mechanisms across multiple kinase inhibitors and developed rational drug-combination approaches that target cross-talk between two signaling…

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Single-molecule probing of the conformational homogeneity of the ABC transporter BtuCD

Posted on Jun 18th, 2018 - By Min Yang

Single-molecule probing of the conformational homogeneity of the ABC transporter BtuCDSingle-molecule probing of the conformational homogeneity of the ABC transporter BtuCD, Published online: 18 June 2018; doi:10.1038/s41589-018-0088-2A single-molecule approach combined with molecular dynamics simulations to examine the conformational dynamics of the Escherichia coli ABC transporter BtuCD defines a coordinated sequence of events leading to unidirectional…

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Scavenging of superoxide by a membrane-bound superoxide oxidase

Posted on Jun 18th, 2018 - By Camilla A. K. Lundgren

Scavenging of superoxide by a membrane-bound superoxide oxidaseScavenging of superoxide by a membrane-bound superoxide oxidase, Published online: 18 June 2018; doi:10.1038/s41589-018-0072-xThe membrane-bound enzyme CybB can directly oxidize superoxide to molecular oxygen and transfer the sequestered electrons to ubiquinone in vitro, providing a mechanism for superoxide scavenging distinct from that of superoxide…

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The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides

Posted on Jun 18th, 2018 - By Vincent Wiebach

The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptidesThe anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides, Published online: 18 June 2018; doi:10.1038/s41589-018-0068-6The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product…

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The Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases

Posted on Jun 18th, 2018 - By Suzana Markolovic

The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPasesThe Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases, Published online: 18 June 2018; doi:10.1038/s41589-018-0071-yStructural, biochemical and cellular studies reveal JMJD7 to be a Jumonji-C oxygenase that catalyzes (3S)-lysyl hydroxylation of the translation factor family of GTPases, DRG1 and…

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Vitamin B<sub>12</sub> import is all about timing

Posted on Jun 18th, 2018 - By Lutz Schmitt

Vitamin B12 import is all about timingVitamin B<sub>12</sub> import is all about timing, Published online: 18 June 2018; doi:10.1038/s41589-018-0087-3Single-molecule techniques combined with molecular dynamics simulations allowed visualization of a surprisingly high level of conformational homogeneity in the transport cycle of an ABC import system, BtuCD-F, and revealed an unexpected tight coupling of distinct conformational states responsible for vitamin B12 binding, transport and…

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Please hold for chaperones

Posted on Jun 18th, 2018 - By Caitlin Deane

Please hold for chaperonesPlease hold for chaperones, Published online: 18 June 2018; doi:10.1038/s41589-018-0092-6Please hold for…

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Tricks for taking up residence

Posted on Jun 18th, 2018 - By Mirella Bucci

Tricks for taking up residenceTricks for taking up residence, Published online: 18 June 2018; doi:10.1038/s41589-018-0094-4Tricks for taking up…

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Stabilizing synapsis

Posted on Jun 18th, 2018 - By Yiyun Song

Stabilizing synapsisStabilizing synapsis, Published online: 18 June 2018; doi:10.1038/s41589-018-0095-3Stabilizing…

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Linkers for protein degradation

Posted on Jun 11th, 2018 - By Philip P. Chamberlain

Linkers for protein degradationLinkers for protein degradation, Published online: 11 June 2018; doi:10.1038/s41589-018-0057-9The ability to subvert E3 ubiquitin ligases with small-molecule drugs offers tremendous promise for drug discovery. A new study demonstrates how structural and computational techniques can engineer and exploit unnatural protein–protein interfaces to design selective protein…

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Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern

Posted on Jun 11th, 2018 - By Benoit Castrec

Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition patternStructural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern, Published online: 11 June 2018; doi:10.1038/s41589-018-0077-5Aided by the solving of the structures of human NMT1 with substrate-mimicking peptides, mapping of human and Arabidopsis myristoylomes defines a myristoylation recognition motif and over 1,000 myristoylated protein…

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Plasticity in binding confers selectivity in ligand-induced protein degradation

Posted on Jun 11th, 2018 - By Radosław P. Nowak

Plasticity in binding confers selectivity in ligand-induced protein degradationPlasticity in binding confers selectivity in ligand-induced protein degradation, Published online: 11 June 2018; doi:10.1038/s41589-018-0055-ySelectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective…

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Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins

Posted on Jun 4th, 2018 - By Jianchao Li

Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrinsPotent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins, Published online: 04 June 2018; doi:10.1038/s41589-018-0082-8Potent pan-Atg8 or GABARAP-selective inhibitory peptides derived from giant neuronal ankyrin-B and -G effectively block autophagy in cell cultures and in C. elegans…

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Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme

Posted on Jun 4th, 2018 - By Nan Wang

Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzymeNatural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme, Published online: 04 June 2018; doi:10.1038/s41589-018-0061-0Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct…

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Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system

Posted on Jun 4th, 2018 - By Tong Xiao

Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine systemCopper regulates rest-activity cycles through the locus coeruleus-norepinephrine system, Published online: 04 June 2018; doi:10.1038/s41589-018-0062-zCopper contributes to regulating zebrafish rest–activity cycles through the locus coeruleus system by modulating the biosynthesis of norepinephrine; brain copper deficiency leads to lower levels of both synaptic norepinephrine and daytime…

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Functional assignment of multiple catabolic pathways for <span class=”small-caps”>d</span>-apiose

Posted on Jun 4th, 2018 - By Michael S. Carter

Functional assignment of multiple catabolic pathways for d-apioseFunctional assignment of multiple catabolic pathways for <span class="small-caps">d</span>-apiose, Published online: 04 June 2018; doi:10.1038/s41589-018-0067-7A bioinformatic strategy beginning with solute-binding proteins involved in sugar transport led to the functional annotation of four previously unknown catabolic pathways of the branched pentose…

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A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis

Posted on May 28th, 2018 - By Xue Chen

A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesisA pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis, Published online: 28 May 2018; doi:10.1038/s41589-018-0059-7Although the conversion of (7S)-salutaridinol 7-O-acetate to thebaine can occur spontaneously, the identification of a thebaine synthase enzyme that catalyzes the reaction indicates how nature avoids the formation of labile hydroxylated…

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Genome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNA

Posted on May 21st, 2018 - By Xiaoting Shu

Genome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNAGenome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNA, Published online: 21 May 2018; doi:10.1038/s41589-018-0065-9A genome-wide uracil profiling technology (termed “dU-seq”), based on selective labeling and biotin pull-down, reveals that uracil is enriched at the centromere of the human…

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Computational redesign of enzymes for regio- and enantioselective hydroamination

Posted on May 21st, 2018 - By Ruifeng Li

Computational redesign of enzymes for regio- and enantioselective hydroaminationComputational redesign of enzymes for regio- and enantioselective hydroamination, Published online: 21 May 2018; doi:10.1038/s41589-018-0053-0Computational protein design, without subsequent directed evolution, rapidly provides a set of aspartase variants capable of biocatalytic asymmetric addition of ammonia to substituted acrylates, producing various enantiopure β-amino…

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Tracking tRNA packages

Posted on May 16th, 2018 - By Achillefs N. Kapanidis

Tracking tRNA packagesTracking tRNA packages, Published online: 16 May 2018; doi:10.1038/s41589-018-0066-8Fast, single-molecule tracking microscopy monitors transitions between mobile and ribosome-bound fluorescent tRNAs to achieve nucleotide-resolution measurements of translation rates in living…

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Buffering transition

Posted on May 16th, 2018 - By Yiyun Song

Buffering transitionBuffering transition, Published online: 16 May 2018; doi:10.1038/s41589-018-0076-6Buffering…

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Electron handoff

Posted on May 16th, 2018 - By Caitlin Deane

Electron handoffElectron handoff, Published online: 16 May 2018; doi:10.1038/s41589-018-0073-9Electron…

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Membrane association of monotopic phosphoglycosyl transferase underpins function

Posted on May 16th, 2018 - By Leah C. Ray

Membrane association of monotopic phosphoglycosyl transferase underpins functionMembrane association of monotopic phosphoglycosyl transferase underpins function, Published online: 16 May 2018; doi:10.1038/s41589-018-0054-zThe structure of a monotopic polyprenol phosphate phosphoglycosyl transferase, PglC, reveals how it interacts with the bacterial membrane and coordinates a reaction between membrane-embedded and soluble substrates during glycoconjugate…

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tRNA tracking for direct measurements of protein synthesis kinetics in live cells

Posted on May 16th, 2018 - By Ivan L. Volkov

tRNA tracking for direct measurements of protein synthesis kinetics in live cellstRNA tracking for direct measurements of protein synthesis kinetics in live cells, Published online: 16 May 2018; doi:10.1038/s41589-018-0063-yCombination of single-molecule tracking experiments and machine-learning approaches to monitor diffusional state transitions between ribosome-bound and free tRNAs allows codon resolution measurements of translation…

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Next-generation biocontainment systems for engineered organisms

Posted on May 16th, 2018 - By Jeong Wook Lee

Next-generation biocontainment systems for engineered organismsNext-generation biocontainment systems for engineered organisms, Published online: 16 May 2018; doi:10.1038/s41589-018-0056-xSynthetic biology offers innovative approaches for engineering biological systems, but also supports the development of biocontainment strategies that ensure the safe application of genetically modified…

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Identification of a <i>S. aureus</i> virulence factor by activity-based protein profiling (ABPP)

Posted on May 16th, 2018 - By Christian S. Lentz

Identification of a S. aureus virulence factor by activity-based protein profiling (ABPP)Identification of a <i>S. aureus</i> virulence factor by activity-based protein profiling (ABPP), Published online: 16 May 2018; doi:10.1038/s41589-018-0060-1ABP profiling identifies uncharacterized S. aureus serine hydrolases, including the surface-localized FphB, which processes lipid ester substrates and is required for infection in vivo. An FphB inhibitor reduces in vivo bacterial…

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Functional phosphorylation

Posted on May 16th, 2018 - By Mirella Bucci

Functional phosphorylationFunctional phosphorylation, Published online: 16 May 2018; doi:10.1038/s41589-018-0075-7Functional…

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Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferases

Posted on May 7th, 2018 - By Weston Kightlinger

Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferasesDesign of glycosylation sites by rapid synthesis and analysis of glycosyltransferases, Published online: 07 May 2018; doi:10.1038/s41589-018-0051-2The GlycoSCORES method, which involves cell-free protein expression and substrate-site profiling of glycosyltransferase enzymes by SAMDI–MS, enables the identification of glycosylation tags for glycoengineering…

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Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells

Posted on May 4th, 2018 - By Aaron H. Nile

Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cellsPublisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells, Published online: 04 May 2018; doi:10.1038/s41589-018-0069-5Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem…

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Publisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET

Posted on May 4th, 2018 - By Daria M. Shcherbakova

Publisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRETPublisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET, Published online: 04 May 2018; doi:10.1038/s41589-018-0070-zPublisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared…

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Shared strategies for β-lactam catabolism in the soil microbiome

Posted on Apr 30th, 2018 - By Terence S. Crofts

Shared strategies for β-lactam catabolism in the soil microbiomeShared strategies for β-lactam catabolism in the soil microbiome, Published online: 30 April 2018; doi:10.1038/s41589-018-0052-1A β-lactamase, a novel type of amidase, and the phenylacetic acid catabolon comprise a catabolic pathway, revealed by genomic and transcriptomic analysis, that enables multiple soil bacteria to use β-lactam antibiotics as a carbon…

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Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET

Posted on Apr 23rd, 2018 - By Daria M. Shcherbakova

Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRETDirect multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET, Published online: 23 April 2018; doi:10.1038/s41589-018-0044-1The monomeric near-infrared (NIR) fluorescent protein miRFP720 enables development of fully NIR Förster resonance energy transfer (FRET) biosensors compatible with CFP–YFP FRET biosensors and blue–green optogenetic tools without optical…

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Evolution of chalcone isomerase from a noncatalytic ancestor

Posted on Apr 23rd, 2018 - By Miriam Kaltenbach

Evolution of chalcone isomerase from a noncatalytic ancestorEvolution of chalcone isomerase from a noncatalytic ancestor, Published online: 23 April 2018; doi:10.1038/s41589-018-0042-3Ancestral sequence inference, directed evolution, structural analysis, NMR, and molecular dynamics simulations illuminate how enantioselective activity arises during the evolutionary trajectory of chalcone isomerase from a noncatalytic…

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Evolution of cyclohexadienyl dehydratase from an ancestral solute-binding protein

Posted on Apr 23rd, 2018 - By Ben E. Clifton

Evolution of cyclohexadienyl dehydratase from an ancestral solute-binding proteinEvolution of cyclohexadienyl dehydratase from an ancestral solute-binding protein, Published online: 23 April 2018; doi:10.1038/s41589-018-0043-2Ancestral protein reconstruction, with structural and biochemical analysis, illustrates the evolution of a solute-binding protein to cyclohexadienyl dehydratase through incorporation of a catalytic residue and gradual reshaping of the binding…

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Generalized extracellular molecule sensor platform for programming cellular behavior

Posted on Apr 23rd, 2018 - By Leo Scheller

Generalized extracellular molecule sensor platform for programming cellular behaviorGeneralized extracellular molecule sensor platform for programming cellular behavior, Published online: 23 April 2018; doi:10.1038/s41589-018-0046-zEngineered erythropoietin receptor scaffolds equipped with extracellular sensor domains and modular intracellular domains that couple to endogenous signaling pathways enable modular reprogramming of designer membrane-bound…

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Spotting the signal

Posted on Apr 16th, 2018 - By Caitlin Deane

Spotting the signalSpotting the signal, Published online: 16 April 2018; doi:10.1038/s41589-018-0047-ySpotting the…

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Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic

Posted on Apr 16th, 2018 - By Marina Santiago

Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibioticGenome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic, Published online: 16 April 2018; doi:10.1038/s41589-018-0041-4Use of a combined Tn-seq and machine-learning approach for predicting mechanisms and targets of antibiotic action in Staphylococcus aureus shows that the natural product lysocin E (LysE) binds Lipid II on the cell surface and damages the…

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Fueled by light

Posted on Apr 16th, 2018 - By Grant Miura

Fueled by lightFueled by light, Published online: 16 April 2018; doi:10.1038/s41589-018-0048-xFueled by…

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The peptide <span class=”small-caps”>d</span>-list

Posted on Apr 16th, 2018 - By Mirella Bucci

The peptide d-listThe peptide <span class="small-caps">d</span>-list, Published online: 16 April 2018; doi:10.1038/s41589-018-0049-9The peptide…

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Structure in sequence

Posted on Apr 16th, 2018 - By Yiyun Song

Structure in sequenceStructure in sequence, Published online: 16 April 2018; doi:10.1038/s41589-018-0050-3Structure in…

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Dynamic coupling between conformations and nucleotide states in DNA gyrase

Posted on Apr 16th, 2018 - By Aakash Basu

Dynamic coupling between conformations and nucleotide states in DNA gyraseDynamic coupling between conformations and nucleotide states in DNA gyrase, Published online: 16 April 2018; doi:10.1038/s41589-018-0037-0Single-molecule measurements of DNA gyrase activity reveal conformational dynamics coupling ATP consumption to DNA…

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Designing macrocyclic disulfide-rich peptides for biotechnological applications

Posted on Apr 16th, 2018 - By Conan K. Wang

Designing macrocyclic disulfide-rich peptides for biotechnological applicationsDesigning macrocyclic disulfide-rich peptides for biotechnological applications, Published online: 16 April 2018; doi:10.1038/s41589-018-0039-yThrough molecular grafting, cyclic disulfide-rich peptides can be used as scaffolds to improve the stability, rigidity, and cellular uptake of bioactive peptides, although a number of factors should be considered when designing such grafted…

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Understanding the Pro/N-end rule pathway

Posted on Apr 16th, 2018 - By David A. Dougan

Understanding the Pro/N-end rule pathwayUnderstanding the Pro/N-end rule pathway, Published online: 16 April 2018; doi:10.1038/s41589-018-0045-0Regulated destruction of proteins underlies just about everything a cell does. A structural study of human Gid4, the N-recognin of the Pro/N-end rule pathway that targets proteins through their N-terminal proline, illuminates the recognition of substrates by this proteolytic…

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Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes

Posted on Apr 2nd, 2018 - By Simon Wisnovsky

Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probesAuthor Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes, Published online: 20 August 2018; doi:10.1038/s41589-018-0040-5Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical…

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FINO<sub>2</sub> initiates ferroptosis through GPX4 inactivation and iron oxidation

Posted on Apr 2nd, 2018 - By Michael M. Gaschler

FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidationFINO<sub>2</sub> initiates ferroptosis through GPX4 inactivation and iron oxidation, Published online: 02 April 2018; doi:10.1038/s41589-018-0031-6FINO2 is a small molecule that requires the endoperoxide moiety and hydroxyl group to promote ferroptosis through indirect inhibition of GPX4 enzymatic function and direct oxidation of iron, resulting in increased lipid…

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Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function

Posted on Apr 2nd, 2018 - By Taka A. Tsunoyama

Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin functionSuper-long single-molecule tracking reveals dynamic-anchorage-induced integrin function, Published online: 02 April 2018; doi:10.1038/s41589-018-0032-5Dissolved oxygen and a reducing-plus-oxidizing system suppress photobleaching and photoblinking in single-molecule tracking experiments, allowing long recordings of CD47 and integrin that showed temporary immobilization within focal…

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The structural organization of substrate loading in iterative polyketide synthases

Posted on Apr 2nd, 2018 - By Dominik A. Herbst

The structural organization of substrate loading in iterative polyketide synthasesThe structural organization of substrate loading in iterative polyketide synthases, Published online: 02 April 2018; doi:10.1038/s41589-018-0026-3The crystal structure and cryo-electron microscopy of the loading/condensing region of a nonreducing polyketide synthase reveals the insertion of a starter-unit acyltransferase into the condensing region and an asymmetrical post-loading…

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Unfolding of a ClC chloride transporter retains memory of its evolutionary history

Posted on Mar 26th, 2018 - By Duyoung Min

Unfolding of a ClC chloride transporter retains memory of its evolutionary historyUnfolding of a ClC chloride transporter retains memory of its evolutionary history, Published online: 26 March 2018; doi:10.1038/s41589-018-0025-4A single-molecule forced unfolding of E. coli chloride transporter ClC-ec1 shows that the N- and C-terminal halves of the protein unfold independently, with exposed polar surfaces stabilized by membrane lipid head groups and…

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Biosynthesis of redox-active metabolites in response to iron deficiency in plants

Posted on Mar 26th, 2018 - By Jakub Rajniak

Biosynthesis of redox-active metabolites in response to iron deficiency in plantsBiosynthesis of redox-active metabolites in response to iron deficiency in plants, Published online: 26 March 2018; doi:10.1038/s41589-018-0019-2The biosynthesis and secretion of redox-active coumarins sideretin and fraxetin in Arabidopsis thaliana enables the plant to acquire iron under nutrient-limited conditions and provides a blueprint for the use of related compounds in other…

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