Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases

Posted on Jul 18th, 2019 - By Matthew Ravalin

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0322-6The C termini sequences recognized by E3 ubiquitin ligase CHIP were identified via a peptide library screen. Caspase cleavage caused the exposure of aspartic acid at the C termini of Tau and caspase-6 that made them accessible to…

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An excreted small molecule promotes <i>C. elegans</i> reproductive development and aging

Posted on Jul 18th, 2019 - By Andreas H. Ludewig

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0321-7Male C. elegans excrete an N-acylated glutamine that acts via evolutionarily conserved nuclear hormone receptor and chemosensory pathways to counteract dauer diapause and accelerate sexual maturation of hermaphrodites, at the cost of shortening hermaphrodite…

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Imaging nonsense

Posted on Jul 18th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0333-3Imaging…

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Pharmacological targeting of the unfolded protein response for disease intervention

Posted on Jul 18th, 2019 - By Claudio Hetz

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0326-2Hetz et al. discuss recent advances in the identification and optimization of small molecules targeting the unfolded protein response and the application of these small molecules in cancers, neurodegeneration and metabolic…

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DNA jumps with CRISPR

Posted on Jul 18th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0335-1DNA jumps with…

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Freedom to bind

Posted on Jul 18th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0332-4Freedom to…

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A programmable DNA-origami platform for studying lipid transfer between bilayers

Posted on Jul 18th, 2019 - By Xin Bian

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0325-3Use of DNA-origami nanostructures to study lipid transfer between closely apposed membrane bilayers supports a model where phospholipids are transferred by extended synaptotagmin 1 between the endoplasmic reticulum and plasma membrane through a shuttle…

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PROSPECTing for drugs

Posted on Jul 18th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0334-2PROSPECTing for…

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Covalent targeting of the vacuolar H<sup>+</sup>-ATPase activates autophagy via mTORC1 inhibition

Posted on Jul 8th, 2019 - By Clive Yik-Sham Chung

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0308-4A covalent ligand that targets C277 of ATP6V1A was identified resulting in enhanced v-ATPase activity, inhibition of mTORC1 signaling, increased lysosomal acidification, activation of autophagy and clearance of toxic protein…

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Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3

Posted on Jul 8th, 2019 - By Jark Böttcher

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0310-xA chemical probe BI-9321 for the PWWP1 domain of NSD3 and its inactive analog were identified. BI-9321 binds to the methyl-lysine binding site, reduces the association of NSD3 with chromatin and inhibits proliferation of acute myeloid leukemia…

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A marine bacterial enzymatic cascade degrades the algal polysaccharide ulvan

Posted on Jul 8th, 2019 - By Lukas Reisky

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0311-9Elucidation of a multi-enzyme pathway for degradation of the polysaccharide ulvan by Formosa agariphila provides tools to use ulvan biomass from marine algal blooms as feedstock for renewable sources of…

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Clearing debris

Posted on Jul 8th, 2019 - By Delong Meng

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0320-8A new small molecule that targets the vacuolar H+-ATPase activates autophagy, inhibits mTORC1 signaling, and displays potential for clearing toxic protein aggregates involved in neurodegenerative…

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Publisher Correction: BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

Posted on Jul 2nd, 2019 - By William Farnaby

Nature Chemical Biology, Published online: 02 July 2019; doi:10.1038/s41589-019-0329-zPublisher Correction: BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC…

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The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis

Posted on Jun 20th, 2019 - By Luca Laraia

Nature Chemical Biology, Published online: 20 June 2019; doi:10.1038/s41589-019-0307-5The cholesterol-transfer protein GRAMD1A is identified as the target of the autophagy inhibitors autogramin-1 and autogramin-2. GRAMD1A is found to be required for autophagosome…

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Lipids lead the way

Posted on Jun 20th, 2019 - By Leslie N. Aldrich

Nature Chemical Biology, Published online: 20 June 2019; doi:10.1038/s41589-019-0309-3Autophagy is a ‘self-eating’ recycling process that maintains cellular homeostasis. Autogramins were identified as small-molecule autophagy inhibitors that target the cholesterol transport protein GRAMD1A, revealing a role for cholesterol in autophagosome…

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Harnessing the anti-cancer natural product nimbolide for targeted protein degradation

Posted on Jun 17th, 2019 - By Jessica N. Spradlin

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0304-8The natural product nimbolide covalently reacts with a functional cysteine of the E3 ubiquitin ligase RNF114, resulting in impaired substrate recognition and degradation, enabling the use of nimbolide for targeted protein…

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Come-hither compounds

Posted on Jun 17th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0316-4Come-hither…

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A small-molecule inhibitor of C5 complement protein

Posted on Jun 17th, 2019 - By Keith Jendza

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0303-9An inhibitor of the complement pathway of the innate immune system targets the human complement component 5 protein (C5) by binding to an interfacial pocket to prevent its proteolytic cleavage by the last enzyme of the complement pathway, C5…

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Stick it to E3s

Posted on Jun 17th, 2019 - By Matthias Brand

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0312-8The limited availability of small-molecule ligands for E3 ubiquitin ligases stymies the development of next-generation degraders. Two recent papers report the identification of novel, covalent and PROTAC-compatible ligands that hijack the previously untargeted ligases RNF114 and…

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Engineering of an oleaginous bacterium for the production of fatty acids and fuels

Posted on Jun 17th, 2019 - By Hye Mi Kim

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0295-5Optimization of triacylglycerol production in the oleaginous bacterium Rhodococcus opacus followed by pathway engineering enables the enhanced production of free fatty acids, fatty acid ethyl esters and long-chain hydrocarbons from…

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The RASER’s edge

Posted on Jun 17th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0317-3The RASER’s…

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Molecular basis for interactions between an acyl carrier protein and a ketosynthase

Posted on Jun 17th, 2019 - By Jacob C. Milligan

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0301-yA combination of crosslinking, X-ray crystallography, NMR, and mutagenesis provide a detailed visualization of the interactions between an acyl carrier protein and β-ketoacyl-ACP-synthase I in the Escherchia coli fatty acid synthase…

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TEThered vitamin C

Posted on Jun 17th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0319-1TEThered vitamin…

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BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

Posted on Jun 10th, 2019 - By William Farnaby

Nature Chemical Biology, Published online: 10 June 2019; doi:10.1038/s41589-019-0294-6A structure-based design allows the development of a potent PROTAC to degrade BAF ATPase subunits SMARCA2 and SMARCA4 via recruitment of E3 ubiquitin ligase VHL and induce cancer cell…

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Author Correction: Mitochondrial metabolism promotes adaptation to proteotoxic stress

Posted on Jun 4th, 2019 - By Peter Tsvetkov

Nature Chemical Biology, Published online: 04 June 2019; doi:10.1038/s41589-019-0315-5Author Correction: Mitochondrial metabolism promotes adaptation to proteotoxic…

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Mitochondrial metabolism promotes adaptation to proteotoxic stress

Posted on May 27th, 2019 - By Peter Tsvetkov

Nature Chemical Biology, Published online: 27 May 2019; doi:10.1038/s41589-019-0291-9Mitochondrial energy metabolism regulates proteotoxic stress tolerance, exposing a newly discovered sensitivity to the small molecule elesclomol, which induces FDX1-mediated, copper-dependent cell…

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Rewiring bacterial two-component systems by modular DNA-binding domain swapping

Posted on May 20th, 2019 - By Sebastian R. Schmidl

Nature Chemical Biology, Published online: 20 May 2019; doi:10.1038/s41589-019-0286-6Rewiring of bacterial two-component systems (TCSs) was achieved by DNA-binding domain swapping of the two largest response regulator families, which enables cross-species porting and provides a tool for identifying ligands for uncharacterized…

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Small-molecule control of antibody N-glycosylation in engineered mammalian cells

Posted on May 20th, 2019 - By Michelle M. Chang

Nature Chemical Biology, Published online: 20 May 2019; doi:10.1038/s41589-019-0288-4Synthetic gene circuits regulated by small molecules have been used to fine-tune glycosyltransferase expression in CHO cells, providing a method to produce therapeutic monoclonal antibodies with precise glycosylation…

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Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision

Posted on May 17th, 2019 - By Woo-Chan Ahn

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0289-3Structural analysis of uracil DNA glycosylases in complex with DNA reveals that conserved H109 acts as a nucleophile to attack the oxocarbenium ion and makes a covalent bond to the abasic site after uracil excision to form a stable…

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Structural and mechanistic basis of mammalian Nudt12 RNA deNADding

Posted on May 17th, 2019 - By Ewa Grudzien-Nogalska

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0293-7Structural and biochemical analyses identify Nudt12 as a novel mRNA deNADing enzyme in mammalian cells, which has a different substrate preference compared to the deNADing enzyme…

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Natural fumigation as a mechanism for volatile transport between flower organs

Posted on May 17th, 2019 - By Benoît Boachon

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0287-5Bioactive sesquiterpenes accumulating in petunia stigmas are synthesized in the floral tube and then transported to the pistil via natural fumigation within the internal airspace of the developing…

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Suicide inactivation of the uracil DNA glycosylase UdgX by covalent complex formation

Posted on May 17th, 2019 - By Jie Tu

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0290-xStructural analysis of uracil DNA glycosylase reveals that its high affinity with DNA substrates derives from a stable intermediate that is formed by conservative H109 in a protruding loop covalently binding to the abasic site after uracil is…

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The new face of nanowires

Posted on May 17th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0299-1The new face of…

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Arrestin-g pain

Posted on May 17th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0300-zArrestin-g…

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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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