Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    It is known that the five carbon platform chemical glutarate can be catabolized by the glutaryl-CoA dehydrogenation pathway. Here, the authors discover an additional glutarate catabolic pathway involving l-2-hydroxyglutarate and show increased glutarate production by blocking both catabolic pathways.

    • Manman Zhang
    • , Chao Gao
    •  & Ping Xu

  • Article
    | Open Access

    Transition-metal catalysis in living cells poses numerous challenges in terms of biocompatibility, and complex stability and reactivity. Here, the authors report a bioorthogonal gold-catalyzed C-C coupling reaction, occurring in living mammalian cells, even in parallel with a ruthenium-catalyzed deallylation reaction.

    • Cristian Vidal
    • , María Tomás-Gamasa
    •  & José L. Mascareñas

  • Article
    | Open Access

    Assembly of higher-order artificial vesicles can unlock new applications. Here, the authors use optical tweezers to construct user-defined 2D and 3D architectures of chemically distinct vesicles and demonstrate inter-vesicle communication and light-enabled compartment merging.

    • Guido Bolognesi
    • , Mark S. Friddin
    •  & Yuval Elani

  • Article
    | Open Access

    Riboswitches on 5′ ends of mRNAs are important for bacterial gene regulation. Here the authors probe the mechanism of a tRNA aminoacylation sensing T-box riboswitch using single-molecule fluorescence microscopy to characterize dynamic solution conformations and heterogeneous tRNA binding kinetics.

    • Krishna C. Suddala
    • , Javier Cabello-Villegas
    •  & Nils G. Walter

  • Article
    | Open Access

    Retention of drugs loaded into liposomes is a major challenge to effective targeted drug delivery. Here, the authors report on the modification of drugs with a glycosidic pH sensitive switch to improve encapsulation and retention of drugs and demonstrate application in an in vivo cancer model.

    • Pierre-Alain Burnouf
    • , Yu-Lin Leu
    •  & Steve R. Roffler

  • Article
    | Open Access

    Bacterial populations communicate with AI-2 signaling molecules, helping to coordinate biofilm development and other group behaviors. Here the authors design a genetic circuit for mammalian cells that allows them to sense bacterial populations and interfere with quorum communication.

    • Ferdinand Sedlmayer
    • , Dennis Hell
    •  & Martin Fussenegger

  • Article
    | Open Access

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor. Here the authors provide insights into PPARγ activation by combining fluorine (19F) NMR and molecular dynamics simulations to characterize the nuclear receptor conformational ensemble in solution and the response of this ensemble to ligand and coregulatory peptide binding.

    • Ian M. Chrisman
    • , Michelle D. Nemetchek
    •  & Travis S. Hughes

  • Article
    | Open Access

    Microviridins belong to the family of ribosomally synthesized and post-translationally modified peptides (RiPPs). Here, the authors discover a microviridin-synthesizing enzyme in a cyanobacterium that modifies multiple core peptides from a single substrate in a distributive and unstrictly directional manner, an unusual biosynthetic logic for RiPPs.

    • Yi Zhang
    • , Kunhua Li
    •  & Yousong Ding

  • Article
    | Open Access

    Some prokaryotes use alternative respiratory chain complexes, such as the alternative complex III (ACIII), to generate energy. Here authors provide the cryoEM structure of ACIII from Rhodothermus marinus which shows the arrangement of cofactors and provides insights into the mechanism for energy transduction.

    • Joana S. Sousa
    • , Filipa Calisto
    •  & Manuela M. Pereira

  • Article
    | Open Access

    Understanding the functions of protein glycosylation critically depends on methods to efficiently enrich glycoproteins from complex samples. Here, the authors develop a strategy using dendrimer-conjugated benzoboroxole to enhance glycopeptide enrichment, providing the basis for more comprehensive glycoprotein analyses.

    • Haopeng Xiao
    • , Weixuan Chen
    •  & Ronghu Wu

  • Article
    | Open Access

    Evidence suggests oligomerisation of G protein-coupled receptors in membranes, but this is controversial. Here, authors use single-molecule and ensemble FRET, and spectroscopy to show that the neurotensin receptor 1 forms multiple dimer conformations that interconvert - “rolling” interfaces.

    • Patricia M. Dijkman
    • , Oliver K. Castell
    •  & Anthony Watts

  • Article
    | Open Access

    Although protein-ligand pairs are useful tools for bioimaging, they are susceptible to enzymatic degradation and interference from endogenous species. Here, the authors show that a synthetic and bioorthogonal cucurbit[7]uril-guest binding pair can be used to visualize proteins in cells, overcoming limitations of protein-based platforms.

    • Kyung Lock Kim
    • , Gihyun Sung
    •  & Kimoon Kim

  • Article
    | Open Access

    Quantitative mass spectrometry enables the proteome-wide assessment of biomolecular binding affinities. While previous approaches mainly focused on protein–small molecule interactions, the authors here present a method to probe protein–DNA and protein–nucleosome binding affinities at proteome scale.

    • Matthew M. Makowski
    • , Cathrin Gräwe
    •  & Michiel Vermeulen

  • Article
    | Open Access

    Meditope-Fab is a peptide-antibody complex potentially useful for drug delivery and diagnostic, but a short half-life prevents its use in vivo. Here the authors engineer the complex to improve its stability, create functionalized antibodies by click chemistry and use them for in vivo tumor imaging.

    • Krzysztof P. Bzymek
    • , James W. Puckett
    •  & John C. Williams

  • Article
    | Open Access

    As a circadian organ, liver functions are regulated by circadian clock. Here, the authors present a comprehensive proteomics landscape of the mouse liver, including transcription factor binding profiles, phosphorylation and ubiquitylation patterns, nuclear and whole proteome, and the transcriptome.

    • Yunzhi Wang
    • , Lei Song
    •  & Chen Ding

  • Article
    | Open Access

    Technologies for identifying receptor-ligand pairs on living cells at physiological conditions remain scarce. Here, the authors develop a mass spectrometry-based ligand receptor capture technology that can identify receptors for a diverse range of ligands at physiological pH with as few as a million cells.

    • Nadine Sobotzki
    • , Michael A. Schafroth
    •  & Bernd Wollscheid

  • Article
    | Open Access

    DNA is found in a dynamic equilibrium between standard Watson-Crick (WC) base pairs and non-standard Hoogsteen (HG) base pairs. Here the authors describe the influence of echinomycin and actinomycin D ligands binding on the HG-WC base pair dynamics in DNA.

    • Yu Xu
    • , James McSally
    •  & Hashim M. Al-Hashimi

  • Article
    | Open Access

    Ubiquitylation of H2B is associated with transcription and regulation of chromatin structure. Here, the authors perform an unbiased screen to identify the role of chromatin modifications on ubiquitylation of H2BK120 and characterize the crosstalk between H2BK120ub and H2A modifications and variants.

    • Felix Wojcik
    • , Geoffrey P. Dann
    •  & Tom W. Muir

  • Article
    | Open Access

    Self-assembling proteins have important applications in industrial technologies, but it is difficult to predict how mutations affect assembly. Here the authors present SyMAPS, coupling comprehensive codon mutagenesis with high-throughput sequencing, and apply it to bacteriophage capsid protein.

    • Emily C. Hartman
    • , Christopher M. Jakobson
    •  & Danielle Tullman-Ercek

  • Article
    | Open Access

    Serine catabolism to formate supplies one-carbon units for biosynthesis. Here the authors show that formate production in murine cancers with high oxidative metabolism exceeds the biosynthetic demand and that high formate levels promotes invasion of cancer cells.

    • Johannes Meiser
    • , Anne Schuster
    •  & Alexei Vazquez

  • Article
    | Open Access

    Fragin is a diazeniumdiolate metabolite with antifungal activity, produced by some bacteria. Here, Jenul et al. show that metal chelation is the molecular basis of fragin’s antifungal activity, and that a gene cluster directing fragin biosynthesis is also involved in the synthesis of a signal molecule.

    • Christian Jenul
    • , Simon Sieber
    •  & Leo Eberl

  • Article
    | Open Access

    Gain-of-function mutants of p53 are important for cancer development and strategies to target specifically these isoforms are being investigated. Here the authors report that USP15 is a deubiquitinase specifically regulating p53-R175H levels that can be targeted by a small molecule.

    • Achuth Padmanabhan
    • , Nicholes Candelaria
    •  & JoAnne S. Richards

  • Article
    | Open Access

    Deubiquitinases are proteases that cleave after the C-terminus of ubiquitin to hydrolyze ubiquitin chains and cleave ubiquitin from substrates. Here the authors describe a reactive-site-centric chemoproteomics approach to studying deubiquitinase activity, and expand the repertoire of known deubiquitinases.

    • David S. Hewings
    • , Johanna Heideker
    •  & Ingrid E. Wertz

  • Article
    | Open Access

    Jumonji-C domain containing protein 5 (JMJD5) is essential for animal development but its catalytic activity has remained elusive so far. Here the authors show that human JMJD5 is an arginyl-hydroxylase and present the cofactor, substrate and product bound JMJD5 crystal structures.

    • Sarah E. Wilkins
    • , Md. Saiful Islam
    •  & Rasheduzzaman Chowdhury

  • Article
    | Open Access

    Matryoshka doll-like, nested vesicles, each containing a different ingredient to a chemical reaction, can serve as microreactors. Here, the authors developed a system in which mixing of the ingredients can be induced by irradiation with ultraviolet light.

    • James W. Hindley
    • , Yuval Elani
    •  & Oscar Ces

  • Article
    | Open Access

    The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMX) synergistically inhibit bacterial tetrahydrofolate biosynthesis, apparently because SMX potentiates TMP activity. Here, Minato et al. identify a metabolic feedback loop in this pathway, revealing that TMP also potentiates SMX activity.

    • Yusuke Minato
    • , Surendra Dawadi
    •  & Anthony D. Baughn

  • Article
    | Open Access

    The authors have previously shown that membrane voltage can influence embryonic patterning during development. Here, the authors computationally model how nicotine disrupts Xenopus embryogenesis by perturbing voltage gradients, and rescue nicotine-inducted defects with HCN2 channel expression.

    • Vaibhav P. Pai
    • , Alexis Pietak
    •  & Michael Levin

  • Article
    | Open Access

    Na+-coupled acid-base membrane transport proteins regulate blood pressure, ion homeostasis and acid-base chemistry. Here the authors present the 3.9 Å resolution cryoEM structure of the sodium-bicarbonate cotransporter NBCe1 and characterize its ion coordination site and ion accessibility pathway with mutagenesis experiments.

    • Kevin W. Huynh
    • , Jiansen Jiang
    •  & Ira Kurtz

  • Article
    | Open Access

    Despite being highly toxic, carbon monoxide (CO) is also essential as an intracellular signalling molecule, but CO-dependent signalling is poorly understood. Here, authors employ spectroscopic and electrophysiology methods and find that CO activates KATP channels via SUR2A, a heme-regulated receptor.

    • Sofia M. Kapetanaki
    • , Mark J. Burton
    •  & Emma Raven

  • Article
    | Open Access

    There is growing evidence that the kinetics of interactions between inhibitors and their targets can strongly impact therapeutic efficacy. Here the authors describe an isothermal titration calorimetry-based method that can rapidly quantify inhibition kinetics and measure sub-nM binding affinities.

    • Justin M. Di Trani
    • , Stephane De Cesco
    •  & Anthony K. Mittermaier

  • Article
    | Open Access

    Glycans, interaction platforms protruding from the surface of cells, are hard to study due to their diverse architecture. Here, the authors present a method to obtain cells carrying defined glycans, which can then be used to find proteins specifically recognizing these tags.

    • Jennie Grace Briard
    • , Hao Jiang
    •  & Peng Wu

  • Article
    | Open Access

    Synthesis of protein-polymer conjugates typically relies on multi-step processes in solution and on challenging purification strategies. Here the authors show a robust synthesis approach which eliminates purification processes by immobilizing proteins reversibly on modified agarose beads before grafting from polymers via ATRP.

    • Hironobu Murata
    • , Sheiliza Carmali
    •  & Alan J. Russell

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