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  • Cuticle thickness affects dynamics of volatile emission from petunia flowers
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-19
    Pan Liao; Shaunak Ray; Benoît Boachon; Joseph H. Lynch; Arnav Deshpande; Scott McAdam; John A. Morgan; Natalia Dudareva
    更新日期:2020-10-19
  • Hijacking protein degradation
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-16

    Targeted protein degradation provides a powerful complement to small-molecule inhibition in modulating protein activity and allows access to otherwise intractable drug targets.

    更新日期:2020-10-17
  • Advanced rules of relays
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-16
    Sonja Lorenz; Katrin Rittinger

    Transfer of ubiquitin onto target proteins requires controlled interplay between E2 conjugating enzymes and E3 ligases. The structure of a trapped E2~Ub/RCR E3 transfer intermediate provides novel insight into the diversity of mechanisms used to fine tune this relay.

    更新日期:2020-10-17
  • A two-pronged attack
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-16
    Joshua J. Feng; Chao Zhang

    Targeted small-molecule inhibition of BRAFV600E faces seemingly insurmountable obstacles in the clinic, such as rapid emergence of drug resistance. A recent study illustrates the potential of an alternative therapeutic strategy via PROTAC-mediated degradation of the oncogenic BRAF.

    更新日期:2020-10-17
  • Reversal of nucleobase methylation by dioxygenases
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-16
    Guo-Liang Xu; Matthias Bochtler

    The repertoire of nucleobase methylation in DNA and RNA, introduced by chemical agents or enzymes, is large. Most methylation can be reversed either directly by restoration of the original nucleobase or indirectly by replacement of the methylated nucleobase with an unmodified nucleobase. In many direct and indirect demethylation reactions, ALKBH (AlkB homolog) and TET (ten eleven translocation) hydroxylases

    更新日期:2020-10-17
  • Peroxisome compartmentalization of a toxic enzyme improves alkaloid production
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-12
    Parbir S. Grewal; Jennifer A. Samson; Jordan J. Baker; Brian Choi; John E. Dueber

    Eukaryotic cells compartmentalize metabolic pathways in organelles to achieve optimal reaction conditions and avoid crosstalk with cytosolic factors. We found that cytosolic expression of norcoclaurine synthase (NCS), the enzyme that catalyzes the first committed reaction in benzylisoquinoline alkaloid biosynthesis, is toxic in Saccharomyces cerevisiae and, consequently, restricts (S)-reticuline production

    更新日期:2020-10-12
  • Discovery of iron-sensing bacterial riboswitches
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-05
    Siladitya Bandyopadhyay; Susmitnarayan Chaudhury; Dolly Mehta; Arati Ramesh

    Despite the central role of iron in biology, our understanding of how cells sense iron is limited to protein-dependent mechanisms. Here, we report the discovery of iron-sensing riboswitches (named Sensei). Present across bacterial phyla, these RNAs reside in the 5′ untranslated regions or within coding regions of messenger RNAs (mRNAs) encoding iron-related proteins. These riboswitches bind the reduced

    更新日期:2020-10-05
  • Sulfated glycans engage the Ang–Tie pathway to regulate vascular development
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-05
    Matthew E. Griffin; Alexander W. Sorum; Gregory M. Miller; William A. Goddard; Linda C. Hsieh-Wilson

    The angiopoietin (Ang)–Tie pathway is essential for the proper maturation and remodeling of the vasculature. Despite its importance in disease, the mechanisms that control signal transduction through this pathway are poorly understood. Here, we demonstrate that heparan sulfate glycosaminoglycans (HS GAGs) regulate Ang–Tie signaling through direct interactions with both Ang ligands and Tie1 receptors

    更新日期:2020-10-05
  • Designer adhesion GPCR tells its signaling story
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-28
    Eugenia V. Gurevich; Vsevolod V. Gurevich

    The ADGRL3 receptor, a member of the adhesion G-protein-coupled receptor family, is implicated in many neurological diseases. Using a novel technique involving controlled proteolysis of the receptor’s extracellular domain, this study demonstrated that ADGRL3 signals via G12/13 G proteins.

    更新日期:2020-09-28
  • CueR activates transcription through a DNA distortion mechanism
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-28
    Chengli Fang; Steven J. Philips; Xiaoxian Wu; Kui Chen; Jing Shi; Liqiang Shen; Juncao Xu; Yu Feng; Thomas V. O’Halloran; Yu Zhang

    The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein–protein interactions, MerR TFs are capable of reshaping promoter DNA. To address the question of which mechanism prevails, we determined

    更新日期:2020-09-28
  • Glucosylation prevents plant defense activation in phloem-feeding insects
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-28
    Osnat Malka; Michael L. A. E. Easson; Christian Paetz; Monika Götz; Michael Reichelt; Beate Stein; Katrin Luck; Aleksa Stanišić; Ksenia Juravel; Diego Santos-Garcia; Lilach L. Mondaca; Simon Springate; John Colvin; Stephan Winter; Jonathan Gershenzon; Shai Morin; Daniel G. Vassão

    The metabolic adaptations by which phloem-feeding insects counteract plant defense compounds are poorly known. Two-component plant defenses, such as glucosinolates, consist of a glucosylated protoxin that is activated by a glycoside hydrolase upon plant damage. Phloem-feeding herbivores are not generally believed to be negatively impacted by two-component defenses due to their slender piercing-sucking

    更新日期:2020-09-28
  • An ultrasensitive biosensor for high-resolution kinase activity imaging in awake mice
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-28
    Jin-Fan Zhang; Bian Liu; Ingie Hong; Albert Mo; Richard H. Roth; Brian Tenner; Wei Lin; Jason Z. Zhang; Rosana S. Molina; Mikhail Drobizhev; Thomas E. Hughes; Lin Tian; Richard L. Huganir; Sohum Mehta; Jin Zhang

    Protein kinases control nearly every facet of cellular function. These key signaling nodes integrate diverse pathway inputs to regulate complex physiological processes, and aberrant kinase signaling is linked to numerous pathologies. While fluorescent protein-based biosensors have revolutionized the study of kinase signaling by allowing direct, spatiotemporally precise kinase activity measurements

    更新日期:2020-09-28
  • Selective regulation of human TRAAK channels by biologically active phospholipids
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-28
    Samantha Schrecke; Yun Zhu; Jacob W. McCabe; Mariah Bartz; Charles Packianathan; Minglei Zhao; Ming Zhou; David Russell; Arthur Laganowsky

    TRAAK is an ion channel from the two-pore domain potassium (K2P) channel family with roles in maintaining the resting membrane potential and fast action potential conduction. Regulated by a wide range of physical and chemical stimuli, the affinity and selectivity of K2P4.1 toward lipids remains poorly understood. Here we show the two isoforms of K2P4.1 have distinct binding preferences for lipids dependent

    更新日期:2020-09-28
  • PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-28
    Bikash Adhikari; Jelena Bozilovic; Mathias Diebold; Jessica Denise Schwarz; Julia Hofstetter; Martin Schröder; Marek Wanior; Ashwin Narain; Markus Vogt; Nevenka Dudvarski Stankovic; Apoorva Baluapuri; Lars Schönemann; Lorenz Eing; Pranjali Bhandare; Bernhard Kuster; Andreas Schlosser; Stephanie Heinzlmeir; Christoph Sotriffer; Stefan Knapp; Elmar Wolf

    The mitotic kinase AURORA-A is essential for cell cycle progression and is considered a priority cancer target. Although the catalytic activity of AURORA-A is essential for its mitotic function, recent reports indicate an additional non-catalytic function, which is difficult to target by conventional small molecules. We therefore developed a series of chemical degraders (PROTACs) by connecting a clinical

    更新日期:2020-09-28
  • Three's company.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-01
    Caitlin Deane

    更新日期:2020-09-25
  • Shifting the balance.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-01
    Grant Miura

    更新日期:2020-09-25
  • Importin pain relief.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-01
    Mirella Bucci

    更新日期:2020-09-25
  • Made fresh in-house.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-10-01
    Yiyun Song

    更新日期:2020-09-25
  • Organelle membrane-specific chemical labeling and dynamic imaging in living cells.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-21
    Tomonori Tamura,Alma Fujisawa,Masaki Tsuchiya,Yuying Shen,Kohjiro Nagao,Shin Kawano,Yasushi Tamura,Toshiya Endo,Masato Umeda,Itaru Hamachi

    Lipids play crucial roles as structural elements, signaling molecules and material transporters in cells. However, the functions and dynamics of lipids within cells remain unclear because of a lack of methods to selectively label lipids in specific organelles and trace their movement by live-cell imaging. We describe here a technology for the selective labeling and fluorescence imaging (microscopic

    更新日期:2020-09-21
  • ARID2 is a pomalidomide-dependent CRL4CRBN substrate in multiple myeloma cells.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-21
    Junichi Yamamoto,Tetsufumi Suwa,Yuki Murase,Shumpei Tateno,Hirotaka Mizutome,Tomoko Asatsuma-Okumura,Nobuyuki Shimizu,Tsutomu Kishi,Shuji Momose,Masahiro Kizaki,Takumi Ito,Yuki Yamaguchi,Hiroshi Handa

    The immunomodulatory drug (IMiD) thalidomide and its derivatives lenalidomide and pomalidomide are therapeutic agents used in the treatment of multiple myeloma. Although pomalidomide offers considerable clinical benefits to patients with lenalidomide-resistant multiple myeloma, the molecular mechanisms underlying its superior efficacy remain unclear. Here we show that ARID2, a component of the polybromo-associated

    更新日期:2020-09-21
  • Uncovering nature's electronics.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-17
    Thomas A Clarke,Marcus J Edwards

    The electrogenic bacterium Geobacter synthesizes conductive extracellular nanowires to facilitate electron transfer that powers respiration. A highly conductive form of these nanowires is now revealed to be composed of oligomers of an 8-heme cytochrome, OmcZ.

    更新日期:2020-09-18
  • Toward spatially resolved metabolomics.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-17
    Bennett W Fox,Frank C Schroeder

    Coherent Raman imaging enables mapping of chemical features at subcellular resolution, setting the stage for tracking lipids and other metabolites in intact living systems.

    更新日期:2020-09-18
  • Bacterial virulence mediated by orthogonal post-translational modification.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-17
    Kaitlin A Chambers,Rebecca A Scheck

    Many bacterial pathogens secrete virulence factors, also known as effector proteins, directly into host cells. These effectors suppress pro-inflammatory host signaling while promoting bacterial infection. A particularly interesting subset of effectors post-translationally modify host proteins using novel chemistry that is not otherwise found in the mammalian proteome, which we refer to as ‘orthogonal

    更新日期:2020-09-18
  • MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-14
    Nichole J Pedowitz,Anna R Batt,Narek Darabedian,Matthew R Pratt

    Many intracellular proteins are modified by N-acetylglucosamine, a post-translational modification termed O-GlcNAc. This modification is found on serine and threonine side chains and has the potential to regulate signaling pathways through interplay with phosphorylation. Here, we discover and characterize one such example. We find that O-GlcNAc levels control the sensitivity of fibroblasts to actin

    更新日期:2020-09-14
  • Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-14
    Xiaofeng Qi,Lucas Friedberg,Ryan De Bose-Boyd,Tao Long,Xiaochun Li

    Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain (CRD) and to several sites in the seven transmembrane helices (7-TMs) of SMO. However, the mechanism by which sterols regulate SMO via multiple sites is unknown. Here we determined the structures of SMO–Gi complexes

    更新日期:2020-09-14
  • A general strategy to red-shift green fluorescent protein-based biosensors.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-14
    Shen Zhang,Hui-Wang Ai

    Compared with green fluorescent protein-based biosensors, red fluorescent protein (RFP)-based biosensors are inherently advantageous because of reduced phototoxicity, decreased autofluorescence and enhanced tissue penetration. However, existing RFP-based biosensors often suffer from small dynamic ranges, mislocalization and undesired photoconversion. In addition, the choice of available RFP-based biosensors

    更新日期:2020-09-14
  • Author Correction: A quantitative method for proteome reallocation using minimal regulatory interventions.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-09
    Gustavo Lastiri-Pancardo,Jonathan S Mercado-Hernández,Juhyun Kim,José I Jiménez,José Utrilla

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-10
  • Optogenetic control of the lac operon for bacterial chemical and protein production.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-07
    Makoto A Lalwani,Samantha S Ip,César Carrasco-López,Catherine Day,Evan M Zhao,Hinako Kawabe,José L Avalos

    Control of the lac operon with isopropyl β-d-1-thiogalactopyranoside (IPTG) has been used to regulate gene expression in Escherichia coli for countless applications, including metabolic engineering and recombinant protein production. However, optogenetics offers unique capabilities, such as easy tunability, reversibility, dynamic induction strength and spatial control, that are difficult to obtain

    更新日期:2020-09-08
  • Pyruvate-responsive genetic circuits for dynamic control of central metabolism.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-07
    Xianhao Xu,Xueliang Li,Yanfeng Liu,Yonglian Zhu,Jianghua Li,Guocheng Du,Jian Chen,Rodrigo Ledesma-Amaro,Long Liu

    Dynamic regulation is a promising strategy for fine-tuning metabolic fluxes in microbial cell factories. However, few of these synthetic regulatory systems have been developed for central carbon metabolites. Here we created a set of programmable and bifunctional pyruvate-responsive genetic circuits for dynamic dual control (activation and inhibition) of central metabolism in Bacillus subtilis. We used

    更新日期:2020-09-08
  • Modulating the microbiota.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-01
    Mirella Bucci

    更新日期:2020-09-01
  • Histones do double duty.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-01
    Caitlin Deane

    更新日期:2020-09-01
  • Repair switches.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-01
    Yiyun Song

    更新日期:2020-09-01
  • Peaking at the right time.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-09-01
    Grant Miura

    更新日期:2020-09-01
  • Covalent inhibition of NSD1 histone methyltransferase.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-31
    Huang Huang,Christina A Howard,Sergei Zari,Hyo Je Cho,Shirish Shukla,Hao Li,Juliano Ndoj,Paula González-Alonso,Caroline Nikolaidis,Joshua Abbott,David S Rogawski,Mykhaylo A Potopnyk,Katarzyna Kempinska,Hongzhi Miao,Trupta Purohit,Andrew Henderson,Anna Mapp,Maria Luisa Sulis,Adolfo Ferrando,Jolanta Grembecka,Tomasz Cierpicki

    The nuclear receptor-binding SET domain (NSD) family of histone methyltransferases is associated with various malignancies, including aggressive acute leukemia with NUP98-NSD1 translocation. While NSD proteins represent attractive drug targets, their catalytic SET domains exist in autoinhibited conformation, presenting notable challenges for inhibitor development. Here, we employed a fragment-based

    更新日期:2020-08-31
  • Bariatric surgery works through a novel bile acid.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-26
    Bethany P Cummings

    Bariatric surgery causes high rates of remission of type 2 diabetes; however, the mechanisms remain unresolved. A new study identifies cholic-acid-7-sulfate as a novel contributor to the metabolic benefits of bariatric surgery and an attractive target for treatment of type 2 diabetes.

    更新日期:2020-08-26
  • A bio-inspired cell-free system for cannabinoid production from inexpensive inputs.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-24
    Meaghan A Valliere,Tyler P Korman,Mark A Arbing,James U Bowie

    Moving cannabinoid production away from the vagaries of plant extraction and into engineered microbes could provide a consistent, purer, cheaper and environmentally benign source of these important therapeutic molecules, but microbial production faces notable challenges. An alternative to microbes and plants is to remove the complexity of cellular systems by employing enzymatic biosynthesis. Here we

    更新日期:2020-08-24
  • Structural basis for antibiotic action of the B1 antivitamin 2'-methoxy-thiamine.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-24
    Fabian Rabe von Pappenheim,Matteo Aldeghi,Brateen Shome,Tadhg Begley,Bert L de Groot,Kai Tittmann

    The natural antivitamin 2′-methoxy-thiamine (MTh) is implicated in the suppression of microbial growth. However, its mode of action and enzyme-selective inhibition mechanism have remained elusive. Intriguingly, MTh inhibits some thiamine diphosphate (ThDP) enzymes, while being coenzymatically active in others. Here we report the strong inhibition of Escherichia coli transketolase activity by MTh and

    更新日期:2020-08-24
  • Channeling a complex question.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-18
    Martin St Maurice

    It is generally believed that large protein complexes provide a catalytic advantage due to substrate channeling between enzymatic domains. However, the structure and function of the pentafunctional AROM complex suggests a noteworthy exception.

    更新日期:2020-08-18
  • Overcoming epigenetic roadblocks.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Maximilian W D Raas,Dick W Zijlmans,Hendrik Marks

    Reprogramming requires resetting the epigenome toward a pluripotent chromatin state. A new chemical screen identifies epigenetic and signaling roadblocks for reprogramming of human somatic cells, with the inhibition of these roadblocks resulting in a more permissive epigenome for reprogramming.

    更新日期:2020-08-18
  • Targeted self-destruction.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Emily Rodrigues,Matthew S Macauley

    Altered glycosylation helps cancer cells evade immune destruction, and targeted remodeling of glycans in vivo offers the ability to reprogram immune responses. A stable chemical linkage between an antibody and neuraminidase enables the targeted destruction of self-associated sialic acids to enhance antitumor immunity.

    更新日期:2020-08-18
  • Permissive epigenomes endow reprogramming competence to transcriptional regulators.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Kee-Pyo Kim,Jinmi Choi,Juyong Yoon,Jan M Bruder,Borami Shin,Jonghun Kim,Marcos J Arauzo-Bravo,Dong Han,Guangming Wu,Dong Wook Han,Johnny Kim,Patrick Cramer,Hans R Schöler

    Identifying molecular and cellular processes that regulate reprogramming competence of transcription factors broadens our understanding of reprogramming mechanisms. In the present study, by a chemical screen targeting major epigenetic pathways in human reprogramming, we discovered that inhibiting specific epigenetic roadblocks including disruptor of telomeric silencing 1-like (DOT1L)-mediated H3K79/K27

    更新日期:2020-08-18
  • Targeted glycan degradation potentiates the anticancer immune response in vivo.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Melissa A Gray,Michal A Stanczak,Natália R Mantuano,Han Xiao,Johan F A Pijnenborg,Stacy A Malaker,Caitlyn L Miller,Payton A Weidenbacher,Julia T Tanzo,Green Ahn,Elliot C Woods,Heinz Läubli,Carolyn R Bertozzi

    Currently approved immune checkpoint inhibitor therapies targeting the PD-1 and CTLA-4 receptor pathways are powerful treatment options for certain cancers; however, most patients across cancer types still fail to respond. Consequently, there is interest in discovering and blocking alternative pathways that mediate immune suppression. One such mechanism is an upregulation of sialoglycans in malignancy

    更新日期:2020-08-18
  • Structural basis for diamide modulation of ryanodine receptor.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Ruifang Ma,Omid Haji-Ghassemi,Dan Ma,Heng Jiang,Lianyun Lin,Li Yao,Arthur Samurkas,Yuxin Li,Yiwen Wang,Peng Cao,Shian Wu,Yan Zhang,Takashi Murayama,Bernard Moussian,Filip Van Petegem,Zhiguang Yuchi

    The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the highest-resolution cryo-electron microscopy (cryo-EM) structure of RyR1 in the open state, in complex with the anthranilic diamide chlorantraniliprole (CHL). The 3.2-Å local resolution map facilitates unambiguous

    更新日期:2020-08-18
  • Targeting a helix-in-groove interaction between E1 and E2 blocks ubiquitin transfer.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Ann M Cathcart,Gregory H Bird,Thomas E Wales,Henry D Herce,Edward P Harvey,Zachary J Hauseman,Catherine E Newman,Utsarga Adhikary,Michelle S Prew,Tun Oo,Susan Lee,John R Engen,Loren D Walensky

    The ubiquitin–proteasome system (UPS) is a highly regulated protein disposal process critical to cell survival. Inhibiting the pathway induces proteotoxic stress and can be an effective cancer treatment. The therapeutic window observed upon proteasomal blockade has motivated multiple UPS-targeting strategies, including preventing ubiquitination altogether. E1 initiates the cascade by transferring ubiquitin

    更新日期:2020-08-18
  • Structural dissimilarity from self drives neoepitope escape from immune tolerance.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Jason R Devlin,Jesus A Alonso,Cory M Ayres,Grant L J Keller,Sara Bobisse,Craig W Vander Kooi,George Coukos,David Gfeller,Alexandre Harari,Brian M Baker

    T-cell recognition of peptides incorporating nonsynonymous mutations, or neoepitopes, is a cornerstone of tumor immunity and forms the basis of new immunotherapy approaches including personalized cancer vaccines. Yet as they are derived from self-peptides, the means through which immunogenic neoepitopes overcome immune self-tolerance are often unclear. Here we show that a point mutation in a non-major

    更新日期:2020-08-18
  • Electric field stimulates production of highly conductive microbial OmcZ nanowires.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Sibel Ebru Yalcin,J Patrick O'Brien,Yangqi Gu,Krystle Reiss,Sophia M Yi,Ruchi Jain,Vishok Srikanth,Peter J Dahl,Winston Huynh,Dennis Vu,Atanu Acharya,Subhajyoti Chaudhuri,Tamas Varga,Victor S Batista,Nikhil S Malvankar

    Multifunctional living materials are attractive due to their powerful ability to self-repair and replicate. However, most natural materials lack electronic functionality. Here we show that an electric field, applied to electricity-producing Geobacter sulfurreducens biofilms, stimulates production of cytochrome OmcZ nanowires with 1,000-fold higher conductivity (30 S cm−1) and threefold higher stiffness

    更新日期:2020-08-18
  • Publisher Correction: G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-17
    Signe Mathiasen,Tiago Palmisano,Nicole A Perry,Hannah M Stoveken,Alex Vizurraga,Dyke P McEwen,Najeah Okashah,Tobias Langenhan,Asuka Inoue,Nevin A Lambert,Gregory G Tall,Jonathan A Javitch

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-17
  • Publisher Correction: A mass spectrometry-based proteome map of drug action in lung cancer cell lines.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-11
    Benjamin Ruprecht,Julie Di Bernardo,Zhao Wang,Xuan Mo,Oleg Ursu,Matthew Christopher,Rafael B Fernandez,Li Zheng,Brian D Dill,Huijun Wang,Yuting Xu,Andy Liaw,Jonathan D Mortison,Nirodhini Siriwardana,Brian Andresen,Meir Glick,James R Tata,Victoria Kutilek,Ivan Cornella-Taracido,An Chi

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-14
  • Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-10
    Mariluz Soula,Ross A Weber,Omkar Zilka,Hanan Alwaseem,Konnor La,Frederick Yen,Henrik Molina,Javier Garcia-Bermudez,Derek A Pratt,Kıvanç Birsoy

    Cancer cells rewire their metabolism and rely on endogenous antioxidants to mitigate lethal oxidative damage to lipids. However, the metabolic processes that modulate the response to lipid peroxidation are poorly defined. Using genetic screens, we compared metabolic genes essential for proliferation upon inhibition of cystine uptake or glutathione peroxidase-4 (GPX4). Interestingly, very few genes

    更新日期:2020-08-10
  • Orthogonal fluorescent chemogenetic reporters for multicolor imaging.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-10
    Alison G Tebo,Benjamien Moeyaert,Marion Thauvin,Irene Carlon-Andres,Dorothea Böken,Michel Volovitch,Sergi Padilla-Parra,Peter Dedecker,Sophie Vriz,Arnaud Gautier

    Spectrally separated fluorophores allow the observation of multiple targets simultaneously inside living cells, leading to a deeper understanding of the molecular interplay that regulates cell function and fate. Chemogenetic systems combining a tag and a synthetic fluorophore provide certain advantages over fluorescent proteins since there is no requirement for chromophore maturation. Here, we present

    更新日期:2020-08-10
  • G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-10
    Signe Mathiasen,Tiago Palmisano,Nicole A Perry,Hannah M Stoveken,Alex Vizurraga,Dyke P McEwen,Najeah Okashah,Tobias Langenhan,Asuka Inoue,Nevin A Lambert,Gregory G Tall,Jonathan A Javitch

    The adhesion G-protein-coupled receptor (GPCR) latrophilin 3 (ADGRL3) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) and substance use in human genetic studies. Knockdown in multiple species leads to hyperlocomotion and altered dopamine signaling. Thus, ADGRL3 is a potential target for treatment of neuropsychiatric disorders that involve dopamine dysfunction

    更新日期:2020-08-10
  • A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-10
    Arkadiy A Bazhin,Riccardo Sinisi,Umberto De Marchi,Aurélie Hermant,Nicolas Sambiagio,Tamara Maric,Ghyslain Budin,Elena A Goun

    Mitochondrial membrane potential (ΔΨm) is a universal selective indicator of mitochondrial function and is known to play a central role in many human pathologies, such as diabetes mellitus, cancer and Alzheimer’s and Parkinson’s diseases. Here, we report the design, synthesis and several applications of mitochondria-activatable luciferin (MAL), a bioluminescent probe sensitive to ΔΨm, and partially

    更新日期:2020-08-10
  • Active turnover of genomic methylcytosine in pluripotent cells.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-10
    Fabio Spada,Sarah Schiffers,Angie Kirchner,Yingqian Zhang,Gautier Arista,Olesea Kosmatchev,Eva Korytiakova,René Rahimoff,Charlotte Ebert,Thomas Carell

    Epigenetic plasticity underpins cell potency, but the extent to which active turnover of DNA methylation contributes to such plasticity is not known, and the underlying pathways are poorly understood. Here we use metabolic labeling with stable isotopes and mass spectrometry to quantitatively address the global turnover of genomic 5-methyl-2′-deoxycytidine (mdC), 5-hydroxymethyl-2′-deoxycytidine (hmdC)

    更新日期:2020-08-10
  • Functional characterization of a PROTAC directed against BRAF mutant V600E.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-10
    Ganna Posternak,Xiaojing Tang,Pierre Maisonneuve,Ting Jin,Hugo Lavoie,Salima Daou,Stephen Orlicky,Theo Goullet de Rugy,Lauren Caldwell,Kin Chan,Ahmed Aman,Michael Prakesch,Gennady Poda,Pavel Mader,Cassandra Wong,Stefan Maier,Julia Kitaygorodsky,Brett Larsen,Karen Colwill,Zhe Yin,Derek F Ceccarelli,Robert A Batey,Mikko Taipale,Igor Kurinov,David Uehling,Jeff Wrana,Daniel Durocher,Anne-Claude Gingras

    The RAF family kinases function in the RAS–ERK pathway to transmit signals from activated RAS to the downstream kinases MEK and ERK. This pathway regulates cell proliferation, differentiation and survival, enabling mutations in RAS and RAF to act as potent drivers of human cancers. Drugs targeting the prevalent oncogenic mutant BRAF(V600E) have shown great efficacy in the clinic, but long-term effectiveness

    更新日期:2020-08-10
  • Prospecting for molecular glues.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-03
    Willem den Besten,J Russell Lipford

    Two recent studies identified CDK12 inhibitors that bind to CDK12–cyclin K complexes and act as molecular glues to stabilize an interaction with the ubiquitin ligase CUL4–DDB1, leading to cyclin K degradation.

    更新日期:2020-08-03
  • Rational discovery of molecular glue degraders via scalable chemical profiling.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-03
    Cristina Mayor-Ruiz,Sophie Bauer,Matthias Brand,Zuzanna Kozicka,Marton Siklos,Hana Imrichova,Ines H Kaltheuner,Elisa Hahn,Kristina Seiler,Anna Koren,Georg Petzold,Michaela Fellner,Christoph Bock,André C Müller,Johannes Zuber,Matthias Geyer,Nicolas H Thomä,Stefan Kubicek,Georg E Winter

    Targeted protein degradation is a new therapeutic modality based on drugs that destabilize proteins by inducing their proximity to E3 ubiquitin ligases. Of particular interest are molecular glues that can degrade otherwise unligandable proteins by orchestrating direct interactions between target and ligase. However, their discovery has so far been serendipitous, thus hampering broad translational efforts

    更新日期:2020-08-03
  • Bariatric surgery reveals a gut-restricted TGR5 agonist with anti-diabetic effects.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-03
    Snehal N Chaudhari,David A Harris,Hassan Aliakbarian,James N Luo,Matthew T Henke,Renuka Subramaniam,Ashley H Vernon,Ali Tavakkoli,Eric G Sheu,A Sloan Devlin

    Bariatric surgery, the most effective treatment for obesity and type 2 diabetes, is associated with increased levels of the incretin hormone glucagon-like peptide-1 (GLP-1) and changes in levels of circulating bile acids. The levels of individual bile acids in the gastrointestinal (GI) tract after surgery have, however, remained largely unstudied. Using ultra-high performance liquid chromatography–mass

    更新日期:2020-08-03
  • Structural basis for RING-Cys-Relay E3 ligase activity and its role in axon integrity.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-03
    Peter D Mabbitt,Andrea Loreto,Marc-André Déry,Adam J Fletcher,Mathew Stanley,Kuan-Chuan Pao,Nicola T Wood,Michael P Coleman,Satpal Virdee

    MYCBP2 is a ubiquitin (Ub) E3 ligase (E3) that is essential for neurodevelopment and regulates axon maintenance. MYCBP2 transfers Ub to nonlysine substrates via a newly discovered RING-Cys-Relay (RCR) mechanism, where Ub is relayed from an upstream cysteine to a downstream substrate esterification site. The molecular bases for E2–E3 Ub transfer and Ub relay are unknown. Whether these activities are

    更新日期:2020-08-03
  • Caught with the drugs.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-01
    Grant Miura

    更新日期:2020-08-01
  • Hot editing sites.
    Nat. Chem. Biol. (IF 12.587) Pub Date : 2020-08-01
    Yiyun Song

    更新日期:2020-08-01
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