Walking over the inflammasome

Posted on May 13th, 2019 - By Oliver Gorka

Walking over the inflammasomeNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0292-8The NLRP3 inflammasome contributes to pathogenic inflammation in a broad range of diseases, making it a highly relevant drug target. Two studies published in this issue found an inhibitor of NLRP3 inflammasome activation to directly bind NLRP3 within its central NACHT domain, interfering with ATP hydrolysis and structural changes critical for NLRP3 oligomerization and subsequent…

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MCC950 closes the active conformation of NLRP3 to an inactive state

Posted on May 13th, 2019 - By Ana Tapia-Abellán

MCC950 closes the active conformation of NLRP3 to an inactive stateNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0278-6MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, inactivates NLRP3, including hyperactive disease-linked mutations, by closing the ‘open’ conformation, thereby preventing conformational changes required for NLRP3…

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Light-based control of metabolic flux through assembly of synthetic organelles

Posted on May 13th, 2019 - By Evan M. Zhao

Light-based control of metabolic flux through assembly of synthetic organellesNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0284-8Optogenetically controlling the assembly of enzyme clusters enhances product formation and specificity during deoxyviolacein biosynthesis by decreasing concentrations of intermediate metabolites and reducing flux through competing…

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MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition

Posted on May 13th, 2019 - By Rebecca C. Coll

MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibitionNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0277-7MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, interacts directly with NLRP3 at the Walker B motif that hydrolyzes ATP, as defined by a protease-susceptibility assay, mutational analysis, and surface plasmon resonance…

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Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme

Posted on May 13th, 2019 - By Juan Pablo Maianti

Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzymeNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0271-0High-throughput screening identifies compounds that target insulin-degrading enzyme (IDE) and X-ray co-crystallography reveals how these compounds block insulin degradation by IDE but support its proteolysis of other substrates, including…

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Author Correction: In-solution enrichment identifies peptide inhibitors of protein–protein interactions

Posted on May 13th, 2019 - By Fayçal Touti

Author Correction: In-solution enrichment identifies peptide inhibitors of protein–protein interactionsNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0302-xAuthor Correction: In-solution enrichment identifies peptide inhibitors of protein–protein…

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Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGpp

Posted on May 10th, 2019 - By Boyuan Wang

Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGppNature Chemical Biology, Published online: 10 May 2019; doi:10.1038/s41589-019-0296-4Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator…

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Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis

Posted on May 6th, 2019 - By Kazuma Sakamoto

Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axisGlycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis, Published online: 06 May 2019; doi:10.1038/s41589-019-0274-xSulfation of chondroitin sulfate and heparan sulfate dictates their abilities to promote axon growth via regulating the binding to the phosphatase PTPRσ and the consequences on phosphorylation of the cortactin component of the autophagy…

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Optical control of sphingosine-1-phosphate formation and function

Posted on Apr 29th, 2019 - By Johannes Morstein

Optical control of sphingosine-1-phosphate formation and functionOptical control of sphingosine-1-phosphate formation and function, Published online: 29 April 2019; doi:10.1038/s41589-019-0269-7A photoswitchable analog of spingosine-1-phosphate (S1P) that allows for modulation of the action of this bioactive lipid exhibits prolonged metabolic stability compared to S1P, activates S1P receptors in cells and mediates nociception in…

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Biosynthesis of a conserved glycolipid anchor for Gram-negative bacterial capsules

Posted on Apr 29th, 2019 - By Liam Doyle

Biosynthesis of a conserved glycolipid anchor for Gram-negative bacterial capsulesBiosynthesis of a conserved glycolipid anchor for Gram-negative bacterial capsules, Published online: 29 April 2019; doi:10.1038/s41589-019-0276-8Reconstitution of β-Kdo-based capsular polysaccharide biosynthesis and crystallographic analysis of KpsC, a glycosyltransferase with two active sites for β-Kdo-glycolipid primer extension, reveal a new glycosyltransferase structural…

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Braking plant endocytosis

Posted on Apr 22nd, 2019 - By Chunhua Zhang

Braking plant endocytosisBraking plant endocytosis, Published online: 22 April 2019; doi:10.1038/s41589-019-0273-yEndocytosis mediates the internalization of proteins and lipids at the plasma membrane and plays essential roles in plant growth and development. A new small molecule enables manipulation of plant endocytosis in an acute and transient…

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Disruption of endocytosis through chemical inhibition of clathrin heavy chain function

Posted on Apr 22nd, 2019 - By Wim Dejonghe

Disruption of endocytosis through chemical inhibition of clathrin heavy chain functionDisruption of endocytosis through chemical inhibition of clathrin heavy chain function, Published online: 22 April 2019; doi:10.1038/s41589-019-0262-1Affinity-based target isolation and X-ray crystallography enabled identification of the non-protonophore ES9-17 as an inhibitor of the clathrin heavy chain in plants, enabling disruption of…

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Under pressure

Posted on Apr 16th, 2019 - By Grant Miura

Under pressureUnder pressure, Published online: 16 April 2019; doi:10.1038/s41589-019-0282-xUnder…

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Scaffold and organism hopping with chemical probes

Posted on Apr 16th, 2019 - By Jürg Gertsch

Scaffold and organism hopping with chemical probesScaffold and organism hopping with chemical probes, Published online: 16 April 2019; doi:10.1038/s41589-019-0275-9Chemical probes that irreversibly inhibit protein function may be used across species to discover proteins. Combining phenotypic screening and activity-based protein profiling, a new study uncovers a discrete lipid signaling pathway regulating lifespan in the worm Caenorhabditis…

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Cannabinoids on the rise

Posted on Apr 16th, 2019 - By Caitlin Deane

Cannabinoids on the riseCannabinoids on the rise, Published online: 16 April 2019; doi:10.1038/s41589-019-0280-zCannabinoids on the…

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Marking histones

Posted on Apr 16th, 2019 - By Yiyun Song

Marking histonesMarking histones, Published online: 16 April 2019; doi:10.1038/s41589-019-0283-9Marking…

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Avoiding the dumpster

Posted on Apr 16th, 2019 - By Grant Miura

Avoiding the dumpsterAvoiding the dumpster, Published online: 16 April 2019; doi:10.1038/s41589-019-0281-yAvoiding the…

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Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding

Posted on Apr 15th, 2019 - By Masaki Okumura

Dynamic assembly of protein disulfide isomerase in catalysis of oxidative foldingDynamic assembly of protein disulfide isomerase in catalysis of oxidative folding, Published online: 15 April 2019; doi:10.1038/s41589-019-0268-8Single-molecule analysis by high-speed atomic force microscopy reveals that oxidized protein disulfide isomerase adopts a dynamic conformation in the absence of substrates and forms face-to-face dimers to accelerate oxidative folding in the presence of…

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CRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AML

Posted on Apr 15th, 2019 - By Michael E. Vinyard

CRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AMLCRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AML, Published online: 15 April 2019; doi:10.1038/s41589-019-0263-0A CRISPR–Cas9 screening-based structure–activity relationship profiling method reveals that LSD1 inhibitors suppress acute myeloid leukemia by disruption of the interaction between LSD1 and GFI1B instead of the enzyme activity of…

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Chemogenetics defines receptor-mediated functions of short chain free fatty acids

Posted on Apr 15th, 2019 - By Daniele Bolognini

Chemogenetics defines receptor-mediated functions of short chain free fatty acidsChemogenetics defines receptor-mediated functions of short chain free fatty acids, Published online: 15 April 2019; doi:10.1038/s41589-019-0270-1A chemogenomic approach to explore activity of the free fatty acid receptor FFA2 independently of the related FFA3 shows that FFA2 in differentiated adipocytes and colonic crypt cells in mice is responsible for regulated lipolysis and GLP-1…

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Structure and functional reselection of the Mango-III fluorogenic RNA aptamer

Posted on Apr 15th, 2019 - By Robert J. Trachman III

Structure and functional reselection of the Mango-III fluorogenic RNA aptamerStructure and functional reselection of the Mango-III fluorogenic RNA aptamer, Published online: 15 April 2019; doi:10.1038/s41589-019-0267-9Structural analysis of Mango-III in complex with fluorophores reveals a globular architecture and a planar conformation of fluorophores. Structure-guided mutation and functional reselection identified two mutants with improved fluorescence…

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Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming

Posted on Apr 8th, 2019 - By Ayyub Ebrahimi

Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogrammingBromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming, Published online: 08 April 2019; doi:10.1038/s41589-019-0264-zA chromatin-focused chemical screen identified CBP/EP300 bromodomain inhibitors as enhancers of reprogramming. These inhibitors decrease histone H3 lysine 27 acetylation, chromatin accessibility and expression of somatic-specific…

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Structure of McsB, a protein kinase for regulated arginine phosphorylation

Posted on Apr 8th, 2019 - By Marcin J. Suskiewicz

Structure of McsB, a protein kinase for regulated arginine phosphorylationStructure of McsB, a protein kinase for regulated arginine phosphorylation, Published online: 08 April 2019; doi:10.1038/s41589-019-0265-yStructural and biochemical characterization of arginine kinase McsB reveals how its phosphagen kinase–like catalytic domain is adapted to target protein substrates while its phosphoarginine-binding domain allosterically controls kinase…

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ARGuing for a new kinase class

Posted on Apr 8th, 2019 - By Titus J. Boggon

ARGuing for a new kinase classARGuing for a new kinase class, Published online: 08 April 2019; doi:10.1038/s41589-019-0272-zArginine protein kinases regulate bacterial signaling cascades through phosphorylation of key arginine residues. Crystal structures of the kinase McsB provide the first glimpse of how these unusual enzymes recognize their protein substrates and are allosterically…

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

Posted on Apr 5th, 2019 - By Ivan L. Volkov

Author Correction: tRNA tracking for direct measurements of protein synthesis kinetics in live cellsAuthor Correction: tRNA tracking for direct measurements of protein synthesis kinetics in live cells, Published online: 05 April 2019; doi:10.1038/s41589-019-0266-xAuthor Correction: tRNA tracking for direct measurements of protein synthesis kinetics in live…

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Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale

Posted on Apr 1st, 2019 - By Steven Schmitt

Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scaleAnalysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale, Published online: 01 April 2019; doi:10.1038/s41589-019-0250-5Combinatorial shuffling of peptide sequence modules, post-translational modification and screening with a high-throughput growth inhibition assay results in the identification of lanthipeptide variants with altered antibacterial…

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Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides

Posted on Apr 1st, 2019 - By Rebecca J. Edgar

Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharidesDiscovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides, Published online: 01 April 2019; doi:10.1038/s41589-019-0251-4Genetic, structural and biochemical analysis identifies GacH as a glycerol phosphate transferase that modifies N-acetylglucosamine components of group A carbohydrates (GAC) in streptococcal cell…

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An orange calcium-modulated bioluminescent indicator for non-invasive activity imaging

Posted on Apr 1st, 2019 - By Younghee Oh

An orange calcium-modulated bioluminescent indicator for non-invasive activity imagingAn orange calcium-modulated bioluminescent indicator for non-invasive activity imaging, Published online: 01 April 2019; doi:10.1038/s41589-019-0256-zOrange CaMBI, a genetically encoded bioluminescent calcium indicator consisting of calcium-sensing domain CaM, luciferase, and fluorescent proteins, reports calcium dynamics in single cells and reveals calcium oscillations in whole mouse…

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Harvesting Moco

Posted on Mar 25th, 2019 - By Ralf R. Mendel

Harvesting MocoHarvesting Moco, Published online: 25 March 2019; doi:10.1038/s41589-019-0257-yThe molybdenum cofactor (Moco) is a fragile prosthetic group essential for most organisms. Nematodes are now capable of extracting Moco from their bacterial diet to mediate detoxification of…

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Pharmacological convergence reveals a lipid pathway that regulates <i>C. elegans</i> lifespan

Posted on Mar 25th, 2019 - By Alice L. Chen

Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespanPharmacological convergence reveals a lipid pathway that regulates <i>C. elegans</i> lifespan, Published online: 25 March 2019; doi:10.1038/s41589-019-0243-4Phenotypic screening identifies a small-molecule inhibitor of the C. elegans serine hydrolase FAAH-4 that promotes longevity and identifies the enzyme as the functional homolog of mammalian monoacylglycerol lipase…

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Cascaded amplifying circuits enable ultrasensitive cellular sensors for toxic metals

Posted on Mar 25th, 2019 - By Xinyi Wan

Cascaded amplifying circuits enable ultrasensitive cellular sensors for toxic metalsCascaded amplifying circuits enable ultrasensitive cellular sensors for toxic metals, Published online: 25 March 2019; doi:10.1038/s41589-019-0244-3An engineered biosensor, which optimizes metal-sensing and couples it to transcriptional amplification cascades that produce a fluorescent protein, was applied to build a sensitive and easy-to-use sensor for the toxic metals As3+ and…

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Molybdenum cofactor transfer from bacteria to nematode mediates sulfite detoxification

Posted on Mar 25th, 2019 - By Kurt Warnhoff

Molybdenum cofactor transfer from bacteria to nematode mediates sulfite detoxificationMolybdenum cofactor transfer from bacteria to nematode mediates sulfite detoxification, Published online: 25 March 2019; doi:10.1038/s41589-019-0249-yThe molybdenum cofactor (Moco) is required for survival to mitigate sulfite toxicity. Genetic studies in C. elegans reveal that Moco-biosynthetic mutants are able to survive if Moco is provided through the microbial…

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Dual phenazine gene clusters enable diversification during biosynthesis

Posted on Mar 18th, 2019 - By Yi-Ming Shi

Dual phenazine gene clusters enable diversification during biosynthesisDual phenazine gene clusters enable diversification during biosynthesis, Published online: 18 March 2019; doi:10.1038/s41589-019-0246-1Enzymes from two discrete biosynthetic gene clusters in the entomopathogenic bacterium Xenorhabdus szentirmaii cooperate to produce a diverse array of phenazine natural products, including phenazine–peptide and phenazine–polyketide…

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New roles for old RNA cap flavors

Posted on Mar 18th, 2019 - By Richard A. Padgett

New roles for old RNA cap flavorsNew roles for old RNA cap flavors, Published online: 18 March 2019; doi:10.1038/s41589-019-0252-3The N6-methyladenosine modification next to the 5′ RNA cap has dynamic regulatory functions. Recent findings show that this modification regulates the splicing and translational activity of different classes of…

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Affinity selection and sequencing

Posted on Mar 18th, 2019 - By Kit S. Lam

Affinity selection and sequencingAffinity selection and sequencing, Published online: 18 March 2019; doi:10.1038/s41589-019-0253-2Powerful combinatorial peptide library methods allow the discovery of peptide leads from diverse libraries. A new platform based on tandem mass spectrometry peptide sequencing coupled with high-performance size-exclusion chromatography enables identification of high-affinity peptidic ligands from focused…

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An appetite for aromatics

Posted on Mar 18th, 2019 - By Mirella Bucci

An appetite for aromaticsAn appetite for aromatics, Published online: 18 March 2019; doi:10.1038/s41589-019-0260-3An appetite for…

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A broken heart can mend

Posted on Mar 18th, 2019 - By Grant Miura

A broken heart can mendA broken heart can mend, Published online: 18 March 2019; doi:10.1038/s41589-019-0259-9A broken heart can…

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A new CRISPR scissor

Posted on Mar 18th, 2019 - By Yiyun Song

A new CRISPR scissorA new CRISPR scissor, Published online: 18 March 2019; doi:10.1038/s41589-019-0261-2A new CRISPR…

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Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy

Posted on Mar 18th, 2019 - By Mehran Dastmalchi

Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppyNeopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy, Published online: 18 March 2019; doi:10.1038/s41589-019-0247-0Neopinone isomerase catalyzes the isomerization of the opiate alkaloid neopinone to codeinone, driving the biosynthesis of codeine and morphine and preventing accumulation of their isomers neopine and…

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A better binder builder

Posted on Mar 18th, 2019 - By Caitlin Deane

A better binder builderA better binder builder, Published online: 18 March 2019; doi:10.1038/s41589-019-0258-xA better binder…

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Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1

Posted on Mar 6th, 2019 - By Jacob I Stuckey

Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1, Published online: 06 March 2019; doi:10.1038/s41589-019-0242-5Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex…

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Potassium channel selectivity filter dynamics revealed by single-molecule FRET

Posted on Mar 4th, 2019 - By Shizhen Wang

Potassium channel selectivity filter dynamics revealed by single-molecule FRETPotassium channel selectivity filter dynamics revealed by single-molecule FRET, Published online: 04 March 2019; doi:10.1038/s41589-019-0240-7Single-molecule FRET shows that a loop, which forms the selectivity filter in the bacterial inwardly rectifying K+ channel KirBac1.1, transitions between constrained and dilated conformations depending on ion occupancy of the…

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Publisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling

Posted on Mar 4th, 2019 - By Agata Nawrotek

Publisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signalingPublisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling, Published online: 04 March 2019; doi:10.1038/s41589-019-0255-0Publisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase…

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A flexible filter maintains a tight grip

Posted on Mar 4th, 2019 - By Adrian Gross

A flexible filter maintains a tight gripA flexible filter maintains a tight grip, Published online: 04 March 2019; doi:10.1038/s41589-019-0248-zPotassium channels allow the passage of potassium ions across membranes at rates approaching the diffusion limit while maintaining exquisite selectivity between ion species. Single-molecule studies now reveal that the selectivity filter of these proteins transitions between different…

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Bidirectional modulation of HIF-2 activity through chemical ligands

Posted on Feb 25th, 2019 - By Dalei Wu

Bidirectional modulation of HIF-2 activity through chemical ligandsBidirectional modulation of HIF-2 activity through chemical ligands, Published online: 25 February 2019; doi:10.1038/s41589-019-0234-5Structural analysis of HIF-2α in complex with agonists and antagonists reveal that chemical ligands regulate the activity of HIF-2α by affecting the stability of the HIF-2α–ARNT heterodimer via redirecting residues in the PAS-B…

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Designing a chemical inhibitor for the AAA protein spastin using active site mutations

Posted on Feb 18th, 2019 - By Tommaso Cupido

Designing a chemical inhibitor for the AAA protein spastin using active site mutationsDesigning a chemical inhibitor for the AAA protein spastin using active site mutations, Published online: 18 February 2019; doi:10.1038/s41589-019-0225-6The AAA protein spastin is needed for cell division and organelle transport. Testing spastin constructs with engineered mutations resulted in the identification of a chemical probe to analyze spastin-specific functions in…

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Tightening a deadly pore former

Posted on Feb 18th, 2019 - By Jialing Lin

Tightening a deadly pore formerTightening a deadly pore former, Published online: 18 February 2019; doi:10.1038/s41589-019-0235-4A small molecule was identified that binds to a unique site on the pro-apoptotic protein BAX, stabilizing the protein structure allosterically and preventing the conformational activation to a pore former by BH3…

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FTO controls reversible m<sup>6</sup>Am RNA methylation during snRNA biogenesis

Posted on Feb 18th, 2019 - By Jan Mauer

FTO controls reversible m6Am RNA methylation during snRNA biogenesisFTO controls reversible m<sup>6</sup>Am RNA methylation during snRNA biogenesis, Published online: 18 February 2019; doi:10.1038/s41589-019-0231-8Two different methylation states of the adenosine adjacent to the snRNA cap are found in the biogenesis process of snRNAs, Am and m6Am, whose levels are regulated by FTO and are related to alternative pre-mRNA…

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Site-specific ubiquitylation and SUMOylation using genetic-code expansion and sortase

Posted on Feb 15th, 2019 - By Maximilian Fottner

Site-specific ubiquitylation and SUMOylation using genetic-code expansion and sortaseSite-specific ubiquitylation and SUMOylation using genetic-code expansion and sortase, Published online: 15 February 2019; doi:10.1038/s41589-019-0227-4A method combining genetic-code expansion, bioorthogonal Staudinger reduction and sortase-mediated transpeptidation enables site-specific and orthogonal modification of proteins with ubiquitin and SUMO in vitro and in living…

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A super-powered S-layer

Posted on Feb 15th, 2019 - By Caitlin Deane

A super-powered S-layerA super-powered S-layer, Published online: 15 February 2019; doi:10.1038/s41589-019-0236-3A super-powered…

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Decoding without the cipher

Posted on Feb 15th, 2019 - By Amit Kumar Singh Gautam

Decoding without the cipherDecoding without the cipher, Published online: 15 February 2019; doi:10.1038/s41589-019-0230-9A new method introduces ubiquitin or ubiquitin-like proteins at specific sites in any protein without the requirement of the cellular ubiquitylation machinery. This will help decipher the code by which these modifications control cellular…

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METTLing with translation

Posted on Feb 15th, 2019 - By Grant Miura

METTLing with translationMETTLing with translation, Published online: 15 February 2019; doi:10.1038/s41589-019-0237-2METTLing with…

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To be or not to be?

Posted on Feb 15th, 2019 - By Yiyun Song

To be or not to be?To be or not to be?, Published online: 15 February 2019; doi:10.1038/s41589-019-0239-0To be or not to…

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Author Correction: Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

Posted on Feb 6th, 2019 - By Yeon Hee Ban

Author Correction: Complete reconstitution of the diverse pathways of gentamicin B biosynthesisAuthor Correction: Complete reconstitution of the diverse pathways of gentamicin B biosynthesis, Published online: 06 February 2019; doi:10.1038/s41589-019-0232-7Author Correction: Complete reconstitution of the diverse pathways of gentamicin B…

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Mechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin system

Posted on Feb 4th, 2019 - By Dukas Jurėnas

Mechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin systemMechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin system, Published online: 04 February 2019; doi:10.1038/s41589-018-0216-zStructural and biochemical analysis of the AtaR–AtaT toxin–antioxin system reveals that AtaR traps AtaT in a precatalytic monomeric state and forms a heterohexameric complex to neutralize AtaT and repress transcription of the…

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Small-molecule allosteric inhibitors of BAX

Posted on Feb 4th, 2019 - By Thomas P. Garner

Small-molecule allosteric inhibitors of BAXSmall-molecule allosteric inhibitors of BAX, Published online: 04 February 2019; doi:10.1038/s41589-018-0223-0Using biochemical and NMR studies, a class of small-molecule inhibitors termed BAX activation inhibitors were found to bind directly to a previously unrecognized pocket of inactive BAX and allosterically inhibit conformational changes in…

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A chemoproteomic portrait of the oncometabolite fumarate

Posted on Feb 4th, 2019 - By Rhushikesh A. Kulkarni

A chemoproteomic portrait of the oncometabolite fumarateA chemoproteomic portrait of the oncometabolite fumarate, Published online: 04 February 2019; doi:10.1038/s41589-018-0217-yChemoproteomic mapping of fumarate sensitive cysteines in a hereditary leiomyomatosis and renal cell carcinoma cell line revealed a critical cysteine in the protein–protein interaction interface of the SWI–SNF…

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A class of highly selective inhibitors bind to an active state of PI3Kγ

Posted on Feb 4th, 2019 - By Gangadhara Gangadhara

A class of highly selective inhibitors bind to an active state of PI3KγA class of highly selective inhibitors bind to an active state of PI3Kγ, Published online: 04 February 2019; doi:10.1038/s41589-018-0215-0Combining X-ray structures, surface plasmon resonance and hydrogen-deuterium exchange–mass spectrometry, a class of highly selective inhibitors was found to bind to an active state of PI3Kγ breaking a conformational ‘lock’ important for activation of…

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Bacterial sensors define intracellular free energies for correct enzyme metalation

Posted on Jan 28th, 2019 - By Deenah Osman

Bacterial sensors define intracellular free energies for correct enzyme metalationBacterial sensors define intracellular free energies for correct enzyme metalation, Published online: 28 January 2019; doi:10.1038/s41589-018-0211-4The sensitivities of a set of bacterial metal-sensing transcriptional regulators explain how a protein, such as the cobalt chelatase CbiK, is metalated with its cognate metal in cells rather than mis-metalated with more tightly binding…

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Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL

Posted on Jan 28th, 2019 - By Christian Schmidl

Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLLCombined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL, Published online: 28 January 2019; doi:10.1038/s41589-018-0205-2Epigenome profiling in combination with imaging-based chemosensitivity and integrative bioinformatic analysis establishes a method for detecting therapy-induced vulnerabilities, as shown here for ibrutinib-treated chronic lymphocytic…

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An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patient

Posted on Jan 28th, 2019 - By Jean Quancard

An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patientAn allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patient, Published online: 28 January 2019; doi:10.1038/s41589-018-0222-1An allosteric inhibitor of the proteolytic activity of the CBM signalosome complex scaffolding protein MALT1 acts as a pharmacological chaperone to stabilize a mutant MALT1 carried by an immunodeficient…

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Freedom of movement

Posted on Jan 21st, 2019 - By Ulrich Rass

Freedom of movementFreedom of movement, Published online: 21 January 2019; doi:10.1038/s41589-019-0224-7Holliday junction resolvases lock dynamic DNA four-way junctions into specific structural conformations for symmetric DNA cleavage. Single-molecule studies now reveal that resolvases can relax their grip, enabling Holliday junction conformer transitions and branch migration in the enzyme-bound…

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Junction resolving enzymes use multivalency to keep the Holliday junction dynamic

Posted on Jan 21st, 2019 - By Ruobo Zhou

Junction resolving enzymes use multivalency to keep the Holliday junction dynamicJunction resolving enzymes use multivalency to keep the Holliday junction dynamic, Published online: 21 January 2019; doi:10.1038/s41589-018-0209-ySingle-molecule analysis reveals a novel binding state of Holliday junction (HJ) resolving enzymes where the enzymes partially dissociate from the HJ and allowing nearly unencumbered HJ dynamics, suggesting coupled branch migration and HJ…

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Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum

Posted on Jan 21st, 2019 - By Xiaoxue Zhou

Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicumSequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum, Published online: 21 January 2019; doi:10.1038/s41589-018-0206-1Assembly of the mycobacterial cell envelope layers, including peptidoglycan (PG) and the mycomembrane (MM), is synchronous during elongation, when a mobile fraction of the MM diffuses into the septum after thinning of the diffusion barrier…

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A new Tar-get for inhibition

Posted on Jan 18th, 2019 - By Mirella Bucci

A new Tar-get for inhibitionA new Tar-get for inhibition, Published online: 18 January 2019; doi:10.1038/s41589-018-0220-3A new Tar-get for…

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Pass it along

Posted on Jan 18th, 2019 - By Yiyun Song

Pass it alongPass it along, Published online: 18 January 2019; doi:10.1038/s41589-018-0221-2Pass it…

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Cutting in choline

Posted on Jan 18th, 2019 - By Caitlin Deane

Cutting in cholineCutting in choline, Published online: 18 January 2019; doi:10.1038/s41589-018-0218-xCutting in…

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Ras tuning

Posted on Jan 18th, 2019 - By Grant Miura

Ras tuningRas tuning, Published online: 18 January 2019; doi:10.1038/s41589-018-0219-9Ras…

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Molecular tools for imaging and recording neuronal activity

Posted on Jan 18th, 2019 - By Wenjing Wang

Molecular tools for imaging and recording neuronal activityMolecular tools for imaging and recording neuronal activity, Published online: 18 January 2019; doi:10.1038/s41589-018-0207-0A collection of genetically encoded tools, each with their own capabilities, limitations and performance characteristics, are available for monitoring and manipulating neuronal activity that could allow visualizing the brain at single-cell…

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Discovery of a ZIP7 inhibitor from a Notch pathway screen

Posted on Jan 14th, 2019 - By Erin Nolin

Discovery of a ZIP7 inhibitor from a Notch pathway screenDiscovery of a ZIP7 inhibitor from a Notch pathway screen, Published online: 14 January 2019; doi:10.1038/s41589-018-0200-7A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress…

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IFITM3 directly engages and shuttles incoming virus particles to lysosomes

Posted on Jan 14th, 2019 - By Jennifer S. Spence

IFITM3 directly engages and shuttles incoming virus particles to lysosomesIFITM3 directly engages and shuttles incoming virus particles to lysosomes, Published online: 14 January 2019; doi:10.1038/s41589-018-0213-2Live-cell imaging and virus trafficking studies show that the host innate immune receptor IFITM3 localizes with endocytic vesicles that fuse with incoming viruses to ultimately enhance their traffic to…

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Selective and reversible modification of kinase cysteines with chlorofluoroacetamides

Posted on Jan 14th, 2019 - By Naoya Shindo

Selective and reversible modification of kinase cysteines with chlorofluoroacetamidesSelective and reversible modification of kinase cysteines with chlorofluoroacetamides, Published online: 14 January 2019; doi:10.1038/s41589-018-0204-3Discovery and exploitation of inherent reaction features of chlorofluoroacetamide (CFA) as a warhead such as low off-target activity and reversible reactivity with cysteine enable specific covalent inhibition of targeted…

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Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

Posted on Jan 14th, 2019 - By Yeon Hee Ban

Complete reconstitution of the diverse pathways of gentamicin B biosynthesisComplete reconstitution of the diverse pathways of gentamicin B biosynthesis, Published online: 14 January 2019; doi:10.1038/s41589-018-0203-4The reconstitution of gentamicin B biosynthesis reveals the existence of multiple new intermediates and branching pathways and enables the identification of factors that contribute to the low levels of the natural product in the native…

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Fast bioelectrical switches

Posted on Jan 14th, 2019 - By Michaela TerAvest

Fast bioelectrical switchesFast bioelectrical switches, Published online: 14 January 2019; doi:10.1038/s41589-018-0212-3Faster-than-transcription control of cellular activities is an important but challenging engineering target. Using split ferredoxins and induced dimerization or conformational changes, newly developed metalloprotein switches provide a fast method to control electron…

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A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase

Posted on Jan 14th, 2019 - By Dhanashree S. Kelkar

A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipaseA chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase, Published online: 14 January 2019; doi:10.1038/s41589-018-0195-0Screening with a small-molecule reactive-oxygen-species generator identifies the serine hydrolase enzyme ABHD12 as a lipase for the proapoptotic oxidized phoshatidylserine (ox-PS) lipids, which trigger production of proinflammatory…

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A genetics-free method for high-throughput discovery of cryptic microbial metabolites

Posted on Jan 7th, 2019 - By Fei Xu

A genetics-free method for high-throughput discovery of cryptic microbial metabolitesA genetics-free method for high-throughput discovery of cryptic microbial metabolites, Published online: 07 January 2019; doi:10.1038/s41589-018-0193-2A combination of elicitor screening to induce expression of silent biosynthetic gene clusters with imaging mass spectrometry to visualize the resulting metabolome enables the discovery of nine cryptic natural…

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<i>Legionella</i> effector SetA as a general O-glucosyltransferase for eukaryotic proteins

Posted on Jan 7th, 2019 - By Ling Gao

Legionella effector SetA as a general O-glucosyltransferase for eukaryotic proteins<i>Legionella</i> effector SetA as a general O-glucosyltransferase for eukaryotic proteins, Published online: 07 January 2019; doi:10.1038/s41589-018-0189-yA chemoenzymatic tagging approach was developed and identified eukaryotic host proteins that are O-glycosylated by SetA from Legionella. The SetA-consensus motif was applied to recombinant proteins yielding a site-specific O-glucosylation…

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Protein circuits reprogram cells

Posted on Jan 7th, 2019 - By Yiqian Wu

Protein circuits reprogram cellsProtein circuits reprogram cells, Published online: 07 January 2019; doi:10.1038/s41589-018-0210-5Two protein circuit systems, split-protease-cleavable orthogonal coiled-coil logic (SPOC logic) and circuits of hacked orthogonal modular proteases (CHOMP), have been developed to permit rapid and logic function-based control of mammalian cellular…

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Activation of silent biosynthetic gene clusters using transcription factor decoys

Posted on Dec 31st, 2018 - By Bin Wang

Activation of silent biosynthetic gene clusters using transcription factor decoysActivation of silent biosynthetic gene clusters using transcription factor decoys, Published online: 31 December 2018; doi:10.1038/s41589-018-0187-0Transcription factor decoys, DNA molecules designed to mimic regulatory DNAs and prevent repressors binding to their DNA targets, are used to achieve de-repression of silent biosynthetic gene clusters, resulting in production of new natural…

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Noncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific manner

Posted on Dec 31st, 2018 - By Corey M. Nemec

Noncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific mannerNoncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific manner, Published online: 31 December 2018; doi:10.1038/s41589-018-0194-1Ten new RNA polymerase II kinases were identified, of these Hrr25 was engineered to enable covalent and noncovalent chemical inhibition in vivo, revealing that this kinase regulates polymerase function at noncoding snoRNA…

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Targeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pair

Posted on Dec 31st, 2018 - By Jingli Hou

Targeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pairTargeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pair, Published online: 31 December 2018; doi:10.1038/s41589-018-0190-5A NO delivery system that depends on the hydrolysis of an alkyl-galactose-conjugated NO prodrug by an engineered galactosidase developed using a ‘bump-and-hole’ strategy enabled targeted delivery of NO to specific…

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Conducting the CTD orchestra

Posted on Dec 31st, 2018 - By Carlos Mario Genes Robles

Conducting the CTD orchestraConducting the CTD orchestra, Published online: 31 December 2018; doi:10.1038/s41589-018-0201-6The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) is post-translationally modified during gene expression. A recent study has identified a CTD kinase, Hrr25, that regulates the termination of noncoding RNA genes by recruiting Rtt103, a key termination…

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Publisher Correction: Shared strategies for β-lactam catabolism in the soil microbiome

Posted on Dec 27th, 2018 - By Terence S. Crofts

Publisher Correction: Shared strategies for β-lactam catabolism in the soil microbiomePublisher Correction: Shared strategies for β-lactam catabolism in the soil microbiome, Published online: 27 December 2018; doi:10.1038/s41589-018-0208-zPublisher Correction: Shared strategies for β-lactam catabolism in the soil…

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Publisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor

Posted on Dec 20th, 2018 - By Martin Audet

Publisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptorPublisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor, Published online: 20 December 2018; doi:10.1038/s41589-018-0214-1Publisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E2…

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Affinity-based capture and identification of protein effectors of the growth regulator ppGpp

Posted on Dec 17th, 2018 - By Boyuan Wang

Affinity-based capture and identification of protein effectors of the growth regulator ppGppAffinity-based capture and identification of protein effectors of the growth regulator ppGpp, Published online: 17 December 2018; doi:10.1038/s41589-018-0183-4A mass-spectrometry-based approach to identify E. coli targets of ppGpp finds 56 putative targets including enzymes involved in nucleotide synthesis, such as PurF, which is directly inhibited by ppGpp, regulating adenosine and guanine nucleotide…

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Structural basis of 7SK RNA 5′-γ-phosphate methylation and retention by MePCE

Posted on Dec 17th, 2018 - By Yuan Yang

Structural basis of 7SK RNA 5′-γ-phosphate methylation and retention by MePCEStructural basis of 7SK RNA 5′-γ-phosphate methylation and retention by MePCE, Published online: 17 December 2018; doi:10.1038/s41589-018-0188-zStructural analysis of the human MePCE methyltransferase domain in complex with 7SK in the presence of SAH or SAM reveals that MePCE has higher affinity for capped 7SK and holds it for subsequent assembly of 7SK…

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Metalloprotein switches that display chemical-dependent electron transfer in cells

Posted on Dec 17th, 2018 - By Joshua T. Atkinson

Metalloprotein switches that display chemical-dependent electron transfer in cellsMetalloprotein switches that display chemical-dependent electron transfer in cells, Published online: 17 December 2018; doi:10.1038/s41589-018-0192-3Designed split ferredoxins, fused to protein fragments that associate under certain conditions such as the presence of rapamycin, enable transcriptional and post-translational control over electron transfer in Escherichia coli cells and…

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The bacteria that move me

Posted on Dec 10th, 2018 - By Mirella Bucci

The bacteria that move meThe bacteria that move me, Published online: 10 December 2018; doi:10.1038/s41589-018-0198-xThe bacteria that move…

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<i>N</i><sup>6-</sup>Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

Posted on Dec 10th, 2018 - By Honghui Ma

N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation<i>N</i><sup>6-</sup>Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation, Published online: 10 December 2018; doi:10.1038/s41589-018-0184-3ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in…

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Design of fast proteolysis-based signaling and logic circuits in mammalian cells

Posted on Dec 10th, 2018 - By Tina Fink

Design of fast proteolysis-based signaling and logic circuits in mammalian cellsDesign of fast proteolysis-based signaling and logic circuits in mammalian cells, Published online: 10 December 2018; doi:10.1038/s41589-018-0181-6Protease-cleavable orthogonal-coiled-coil-based (SPOC) systems, in which split viral proteases are activated by small molecules and cleave coiled-coil protease substrates, reprogram signaling with rapid kinetics in mammalian…

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Lanthanide lover

Posted on Dec 10th, 2018 - By Caitlin Deane

Lanthanide loverLanthanide lover, Published online: 10 December 2018; doi:10.1038/s41589-018-0196-zLanthanide…

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E2 enzymes: lessons in ubiquitin transfer from XLID patients

Posted on Dec 10th, 2018 - By Martina Foglizzo

E2 enzymes: lessons in ubiquitin transfer from XLID patientsE2 enzymes: lessons in ubiquitin transfer from XLID patients, Published online: 10 December 2018; doi:10.1038/s41589-018-0191-4Characterization of a novel mutation in the E2 ubiquitin-conjugating enzyme UBE2A accounts for the decreased activity of the mutant enzyme that underlies disease and provides important insight into the catalytic mechanism of…

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Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability

Posted on Dec 10th, 2018 - By Juliana Ferreira de Oliveira

Mechanistic insights revealed by a UBE2A mutation linked to intellectual disabilityMechanistic insights revealed by a UBE2A mutation linked to intellectual disability, Published online: 10 December 2018; doi:10.1038/s41589-018-0177-2Structural and biochemical analysis of a UBE2A mutation linked to intellectual disability reveals that the Q93E mutant perturbs the E2 catalytic microenvironment essential for lysine deprotonation during the ubiquitin-transfer…

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<i>N</i><sup>6</sup>-mA condenses chromatin

Posted on Dec 10th, 2018 - By Yiyun Song

N6-mA condenses chromatin<i>N</i><sup>6</sup>-mA condenses chromatin, Published online: 10 December 2018; doi:10.1038/s41589-018-0199-9N6-mA condenses…

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Riboregulated toehold-gated gRNA for programmable CRISPR–Cas9 function

Posted on Dec 10th, 2018 - By Ka-Hei Siu

Riboregulated toehold-gated gRNA for programmable CRISPR–Cas9 functionRiboregulated toehold-gated gRNA for programmable CRISPR–Cas9 function, Published online: 10 December 2018; doi:10.1038/s41589-018-0186-1Engineering of toehold-gated guide RNA (thgRNA) by tethering toehold riboswitches to sgRNAs enables the activation of CRISPR–Cas9 genome editing or transcriptional regulation in response to complementary synthetic or endogenous cellular…

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Ligand binding to human prostaglandin E receptor EP<sub>4</sub> at the lipid-bilayer interface

Posted on Dec 3rd, 2018 - By Yosuke Toyoda

Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interfaceLigand binding to human prostaglandin E receptor EP<sub>4</sub> at the lipid-bilayer interface, Published online: 03 December 2018; doi:10.1038/s41589-018-0131-3The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among…

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Structural basis for ligand recognition of the human thromboxane A<sub>2</sub> receptor

Posted on Dec 3rd, 2018 - By Hengxin Fan

Structural basis for ligand recognition of the human thromboxane A2 receptorStructural basis for ligand recognition of the human thromboxane A<sub>2</sub> receptor, Published online: 03 December 2018; doi:10.1038/s41589-018-0170-9Structures of the human thromboxane A2 receptor, a member of the prostanoid family of G-protein-coupled receptors, in complex with two synthetic antagonists reveal that ligands access the ligand-binding pocket from the plane of the lipid…

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Crystal structure of the endogenous agonist-bound prostanoid receptor EP3

Posted on Dec 3rd, 2018 - By Kazushi Morimoto

Crystal structure of the endogenous agonist-bound prostanoid receptor EP3Crystal structure of the endogenous agonist-bound prostanoid receptor EP3, Published online: 03 December 2018; doi:10.1038/s41589-018-0171-8Structural analysis of prostaglandin E receptor EP3, a member of the prostanoid receptor subfamily of GPCRs, in complex with the endogenous agonist PGE2 reveals important interactions and motions required for receptor…

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Structures shed light on prostanoid signaling

Posted on Dec 3rd, 2018 - By Kaspar Hollenstein

Structures shed light on prostanoid signalingStructures shed light on prostanoid signaling, Published online: 03 December 2018; doi:10.1038/s41589-018-0178-1Prostanoids signal through G-protein-coupled receptors to regulate diverse physiological processes. Structures of three prostanoid receptors in inactive and active conformations now uncover the molecular determinants of ligand recognition and receptor activation and offer new opportunities for drug…

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Crystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor

Posted on Dec 3rd, 2018 - By Martin Audet

Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptorCrystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor, Published online: 03 December 2018; doi:10.1038/s41589-018-0160-yA structure of the prostaglandin E2 receptor 3 (EP3) bound to the agonist misoprostol shows a completely enclosed binding pocket with a structured water molecule that coordinates misoprostol's ring structure and explains the receptor's…

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