Brief Communications

  • Brief Communication |

    A metabolic labeling method reveals that genomic N6-methyl-deoxyadenosine in mammalian cell lines originates not from direct methylation in DNA, but from a misincorporation of the metabolite of ribo-N6-methyladenosine.

    • Michael U. Musheev
    • , Anne Baumgärtner
    • , Laura Krebs
    •  & Christof Niehrs
  • Brief Communication |

    The authors used an expanded genetic code to incorporate sulfated tyrosine into specific sites of proteins expressed in E. coli and mammalian cells and showed that sulfation of tyrosine at different sites had different functions.

    • James S. Italia
    • , Jennifer C. Peeler
    • , Christen M. Hillenbrand
    • , Christopher Latour
    • , Eranthie Weerapana
    •  & Abhishek Chatterjee
  • Brief Communication |

    Structural and mutational analysis of three homologous cyclases involved in the biosynthesis of iboga and aspidosperma alkaloids reveals how they convert a common substrate into three distinct scaffolds by controlling regio- and stereoselectivity.

    • Lorenzo Caputi
    • , Jakob Franke
    • , Kate Bussey
    • , Scott C. Farrow
    • , Ivo Jose Curcino Vieira
    • , Clare E. M. Stevenson
    • , David M. Lawson
    •  & Sarah E. O’Connor
  • Brief Communication |

    In depsipeptide synthetases, intact adenylation and ketoreductase domains responsible for selecting and reducing α-keto acids are flanked by two halves of a split pseudo-Asub domain whose physical interaction is critical for the module's activity.

    • Diego A. Alonzo
    • , Clarisse Chiche-Lapierre
    • , Michael J. Tarry
    • , Jimin Wang
    •  & T. Martin Schmeing
  • Brief Communication |

    The authors designed a chemical probe, azido-kethoxal, to specifically label guanosine in single-strand RNAs in live cells that could be used to determine transcriptome-wide RNA secondary structures.

    • Xiaocheng Weng
    • , Jing Gong
    • , Yi Chen
    • , Tong Wu
    • , Fang Wang
    • , Shixi Yang
    • , Yushu Yuan
    • , Guanzheng Luo
    • , Kai Chen
    • , Lulu Hu
    • , Honghui Ma
    • , Pingluan Wang
    • , Qiangfeng Cliff Zhang
    • , Xiang Zhou
    •  & Chuan He
  • Brief Communication |

    A transient interaction between 14-3-3ζ and a loop of PTP1B is detected following PTP1B inactivation by reversible oxidation.

    • Avinash D. Londhe
    • , Alexandre Bergeron
    • , Stephanie M. Curley
    • , Fuming Zhang
    • , Keith D. Rivera
    • , Akaash Kannan
    • , Gérald Coulis
    • , Syed H. M. Rizvi
    • , Seung Jun Kim
    • , Darryl J. Pappin
    • , Nicholas K. Tonks
    • , Robert J. Linhardt
    •  & Benoit Boivin
  • Brief Communication |

    The topology of homodimeric membrane protein EmrE is dynamic and includes unassisted flipping of an N-terminal helix in and out of the membrane long after co-translational insertion. Dimerization locks the helix to limit topological dynamics.

    • Maximilian Seurig
    • , Moira Ek
    • , Gunnar von Heijne
    •  & Nir Fluman
  • Brief Communication |

    A 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 complex.

    • Jacob C. Milligan
    • , D. John Lee
    • , David R. Jackson
    • , Andrew J. Schaub
    • , Joris Beld
    • , Jesus F. Barajas
    • , Joseph J. Hale
    • , Ray Luo
    • , Michael D. Burkart
    •  & Shiou-Chuan Tsai
  • Brief Communication |

    An 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 convertase.

    • Keith Jendza
    • , Mitsunori Kato
    • , Michael Salcius
    • , Honnappa Srinivas
    • , Andrea De Erkenez
    • , Anh Nguyen
    • , Doug McLaughlin
    • , Celine Be
    • , Christian Wiesmann
    • , Jason Murphy
    • , Philippe Bolduc
    • , Muneto Mogi
    • , Jose Duca
    • , Abdel Namil
    • , Michael Capparelli
    • , Veronique Darsigny
    • , Erik Meredith
    • , Ritesh Tichkule
    • , Luciana Ferrara
    • , Jessica Heyder
    • , Fang Liu
    • , Patricia A. Horton
    • , Michael J. Romanowski
    • , Markus Schirle
    • , Nello Mainolfi
    • , Karen Anderson
    •  & Gregory A. Michaud
  • Brief Communication |

    MCC950, 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 activation.

    • Ana Tapia-Abellán
    • , Diego Angosto-Bazarra
    • , Helios Martínez-Banaclocha
    • , Carlos de Torre-Minguela
    • , Jose P. Cerón-Carrasco
    • , Horacio Pérez-Sánchez
    • , Juan I. Arostegui
    •  & Pablo Pelegrin
  • Brief Communication |

    MCC950, 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 analysis.

    • Rebecca C. Coll
    • , James R. Hill
    • , Christopher J. Day
    • , Alina Zamoshnikova
    • , Dave Boucher
    • , Nicholas L. Massey
    • , Jessica L. Chitty
    • , James A. Fraser
    • , Michael P. Jennings
    • , Avril A. B. Robertson
    •  & Kate Schroder
  • Brief Communication |

    Orange 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 organs.

    • Younghee Oh
    • , Yunhee Park
    • , Julia H. Cho
    • , Haodi Wu
    • , Nicole K. Paulk
    • , Lan Xiang Liu
    • , Namdoo Kim
    • , Mark A. Kay
    • , Joseph C. Wu
    •  & Michael Z. Lin
  • Brief Communication |

    A chemoenzymatic tagging approach was developed and identified eukaryotic host proteins that are O-glycosylated by SetA from Legionella. The SetA-consensus motif was applied to recombinant proteins yielding a site-specific O-glucosylation method.

    • Ling Gao
    • , Qitao Song
    • , Hao Liang
    • , Yuntao Zhu
    • , Tiantian Wei
    • , Na Dong
    • , Junyu Xiao
    • , Feng Shao
    • , Luhua Lai
    •  & Xing Chen
  • Brief Communication |

    Transcription factor decoys, DNA molecules designed to mimic regulatory DNAs and prevent repressors binding to their DNA targets, are used to achieve de-repression of silent biosynthetic gene clusters, resulting in production of new natural products.

    • Bin Wang
    • , Fang Guo
    • , Shi-Hui Dong
    •  & Huimin Zhao
  • Brief Communication |

    Engineering of toehold-gated guide RNA (thgRNA) by tethering toehold riboswitches to sgRNAs enables the activation of CRISPR–Cas9 genome editing or transcriptional regulation in response to complementary synthetic or endogenous cellular RNAs.

    • Ka-Hei Siu
    •  & Wilfred Chen
  • Brief Communication |

    Structural analysis of prostaglandin E receptor EP3, a member of the prostanoid receptor subfamily of GPCRs, in complex with the endogenous agonist PGE2 reveals important interactions and motions required for receptor activation.

    • Kazushi Morimoto
    • , Ryoji Suno
    • , Yunhong Hotta
    • , Keitaro Yamashita
    • , Kunio Hirata
    • , Masaki Yamamoto
    • , Shuh Narumiya
    • , So Iwata
    •  & Takuya Kobayashi
  • Brief Communication |

    Plant-associated rhizosphere bacteria produce gramibactin, a cyclic lipodepsipeptide siderophore that tightly binds iron via an unexpected functional group, the N-nitrosohydroxylamine (diazeniumdiolate) moieties of the amino acid graminine.

    • Ron Hermenau
    • , Keishi Ishida
    • , Sofia Gama
    • , Bianca Hoffmann
    • , Michel Pfeifer-Leeg
    • , Winfried Plass
    • , Jan Frieder Mohr
    • , Thomas Wichard
    • , Hans-Peter Saluz
    •  & Christian Hertweck
  • Brief Communication |

    Histone H3 serine 10 is found to be the major chromatin acceptor residue for DNA damage–induced ADP-ribosylation and is blocked by specific acetylation sites on PARP1 and/or H3.

    • Glen Liszczak
    • , Katharine L. Diehl
    • , Geoffrey P. Dann
    •  & Tom W. Muir
  • Brief Communication |

    A photoswitchable probe to control Ca2+ influx through L-type Ca2+ channels is useful in pancreatic β cells and can be employed to modulate beating rate in explanted hearts.

    • Timm Fehrentz
    • , Florian M. E. Huber
    • , Nina Hartrampf
    • , Tobias Bruegmann
    • , James A. Frank
    • , Nicholas H. F. Fine
    • , Daniela Malan
    • , Johann G. Danzl
    • , Denis B. Tikhonov
    • , Martin Sumser
    • , Philipp Sasse
    • , David J. Hodson
    • , Boris S. Zhorov
    • , Nikolaj Klöcker
    •  & Dirk Trauner
  • Brief Communication |

    Three homologous cytochrome P450s from monoterpene indole alkaloid-producing plants enable the identification of sarpagan bridge enzyme, which catalyzes either cyclization or aromatization to yield sarpagan or β-carboline alkaloids, respectively.

    • Thu-Thuy T. Dang
    • , Jakob Franke
    • , Ines Soares Teto Carqueijeiro
    • , Chloe Langley
    • , Vincent Courdavault
    •  & Sarah E. O’Connor
  • Brief Communication |

    The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product class.

    • Vincent Wiebach
    • , Andi Mainz
    • , Mary-Ann J. Siegert
    • , Natalia A. Jungmann
    • , Guillaume Lesquame
    • , Sophie Tirat
    • , Assia Dreux-Zigha
    • , Jozsef Aszodi
    • , Dominique Le Beller
    •  & Roderich D. Süssmuth
  • Brief Communication |

    The structure of a monotopic polyprenol phosphate phosphoglycosyl transferase, PglC, reveals how it interacts with the bacterial membrane and coordinates a reaction between membrane-embedded and soluble substrates during glycoconjugate assembly.

    • Leah C. Ray
    • , Debasis Das
    • , Sonya Entova
    • , Vinita Lukose
    • , Andrew J. Lynch
    • , Barbara Imperiali
    •  & Karen N. Allen
  • Brief Communication |

    The crystal structure of a methyltransferase domain embedded within an interrupted adenylation domain provides insight into how a nonribosomal peptide synthetase N-methylates amino acid precursors for their incorporation into the peptide product.

    • Shogo Mori
    • , Allan H. Pang
    • , Taylor A. Lundy
    • , Atefeh Garzan
    • , Oleg V. Tsodikov
    •  & Sylvie Garneau-Tsodikova
  • Brief Communication |

    The discovery of cytochrome P450 monooxygenases that catalyze oxidative demethylation of 6-O-methyl-d-galactose reveals a new activity of cytochrome P450 enzymes and their role in polysaccharide biomass degradation in marine bacteria.

    • Lukas Reisky
    • , Hanna C. Büchsenschütz
    • , Jennifer Engel
    • , Tao Song
    • , Thomas Schweder
    • , Jan-Hendrik Hehemann
    •  & Uwe T. Bornscheuer
  • Brief Communication |

    A de novo–designed protein, Syn-F4, hydrolyzes the siderophore ferric enterobactin both in vitro and in Escherichia coli cells, enabling a bacterial strain lacking the essential natural enterobactin esterase to grow in iron-limited medium.

    • Ann E Donnelly
    • , Grant S Murphy
    • , Katherine M Digianantonio
    •  & Michael H Hecht
  • Brief Communication |

    In Pseudoalteromonas rubra, an unclustered biosynthetic gene encodes a di-iron oxygenase-like enzyme that catalyzes regiospecific C–H activation and cyclization of prodigiosin, yet is unrelated to the Rieske oxygenases that produce other cyclized prodiginines.

    • Tristan de Rond
    • , Parker Stow
    • , Ian Eigl
    • , Rebecca E Johnson
    • , Leanne Jade G Chan
    • , Garima Goyal
    • , Edward E K Baidoo
    • , Nathan J Hillson
    • , Christopher J Petzold
    • , Richmond Sarpong
    •  & Jay D Keasling
  • Brief Communication |

    A toxic conformation of disease-linked huntingtin protein with expanded polyQ is degraded more slowly than the other conformations, as it is less able to engage the autophagy machinery, explaining its higher toxicity compared to other conformations.

    • Yuhua Fu
    • , Peng Wu
    • , Yuyin Pan
    • , Xiaoli Sun
    • , Huiya Yang
    • , Marian Difiglia
    •  & Boxun Lu
  • Brief Communication |

    A nonribosomal peptide synthetase involved in colibactin biosynthesis utilizes S-adenosylmethionine as a nonproteinogenic amino acid building block, which is then converted into the cyclopropane moiety that is critical for colibactin's genotoxic activity.

    • Li Zha
    • , Yindi Jiang
    • , Matthew T Henke
    • , Matthew R Wilson
    • , Jennifer X Wang
    • , Neil L Kelleher
    •  & Emily P Balskus
  • Brief Communication |

    Cpf1 is a CRISPR effector protein that exhibits greater genome editing specificity than Cas9 nuclease. Cpf1 from two distinct bacteria selectively processes RNA polymerase II transcripts into crRNA fragments competent for genome editing.

    • Guocai Zhong
    • , Haimin Wang
    • , Yujun Li
    • , Mai H Tran
    •  & Michael Farzan
  • Brief Communication |

    Characterization of the heme-dependent enzyme KtzT reveals it to be the elusive enzyme responsible for nitrogen–nitrogen bond formation during the biosynthesis of piperazate, a building block for some nonribosomal peptide natural products.

    • Yi-Ling Du
    • , Hai-Yan He
    • , Melanie A Higgins
    •  & Katherine S Ryan
  • Brief Communication |

    A genetically encoded unnatural amino acid analog and its acidic deprotection enable the site-specific incorporation of phosphotyrosine (pTyr) into proteins such as ubiquitin, where it can be used to study the function of this phosphorylated residue.

    • Christian Hoppmann
    • , Allison Wong
    • , Bing Yang
    • , Shuwei Li
    • , Tony Hunter
    • , Kevan M Shokat
    •  & Lei Wang
  • Brief Communication |

    Characterization of the gene cluster for omphalotin biosynthesis reveals that they are ribosomally synthesized peptides whose internal α-N-methyl groups are installed by a methyltransferase fused to the precursor peptide substrate.

    • Niels S van der Velden
    • , Noemi Kälin
    • , Maximilian J Helf
    • , Jörn Piel
    • , Michael F Freeman
    •  & Markus Künzler
  • Brief Communication |

    A synthetic biology system composed of light-wavelength-responsive genetic regulators, signal-processing circuits and pigment-production pathways have resulted in an Escherichia coli strain that can record color images in RGB format.

    • Jesus Fernandez-Rodriguez
    • , Felix Moser
    • , Miryoung Song
    •  & Christopher A Voigt
  • Brief Communication |

    Most microbial biosynthetic gene clusters are inactive under laboratory culture conditions. A CRISPR–Cas9 genome-editing approach in Streptomyces species enables the targeted activation of silent gene clusters and production of encoded natural products.

    • Mingzi M Zhang
    • , Fong Tian Wong
    • , Yajie Wang
    • , Shangwen Luo
    • , Yee Hwee Lim
    • , Elena Heng
    • , Wan Lin Yeo
    • , Ryan E Cobb
    • , Behnam Enghiad
    • , Ee Lui Ang
    •  & Huimin Zhao
  • Brief Communication |

    Crystallographic analysis of human O-GlcNAc hydrolase (hOGA) fragments containing the catalytic domain, including structures in complex with known inhibitors, suggests that OGA is functional as a dimer and defines opportunities for structure-based drug design.

    • Nathaniel L Elsen
    • , Sangita B Patel
    • , Rachael E Ford
    • , Dawn L Hall
    • , Fred Hess
    • , Hari Kandula
    • , Maria Kornienko
    • , John Reid
    • , Harold Selnick
    • , Jennifer M Shipman
    • , Sujata Sharma
    • , Kevin J Lumb
    • , Stephen M Soisson
    •  & Daniel J Klein
  • Brief Communication |

    Crystal structures of human O-GlcNAc hydrolase (hOGA) fragments show that hOGA's dimeric structure is organized by swapping of an α-helical element and reveal features of inhibitor binding to the catalytic domain.

    • Christian Roth
    • , Sherry Chan
    • , Wendy A Offen
    • , Glyn R Hemsworth
    • , Lianne I Willems
    • , Dustin T King
    • , Vimal Varghese
    • , Robert Britton
    • , David J Vocadlo
    •  & Gideon J Davies
  • Brief Communication |

    Characterization of a family of Stigonematales (Stig) cyclases that catalyze stereoselective intramolecular C–C bond formation reveals the enzymatic origins of the complex stereochemical patterns in hapalindole and fischerindole alkaloids.

    • Shasha Li
    • , Andrew N Lowell
    • , Sean A Newmister
    • , Fengan Yu
    • , Robert M Williams
    •  & David H Sherman
  • Brief Communication |

    An automated method for solid-phase polypeptide synthesis capitalizes on rapid amide bond formation to enable the production of multiple traditionally difficult-to-synthesize sequences with both high yield and high purity.

    • Alexander J Mijalis
    • , Dale A Thomas III
    • , Mark D Simon
    • , Andrea Adamo
    • , Ryan Beaumont
    • , Klavs F Jensen
    •  & Bradley L Pentelute
  • Brief Communication |

    Integration of heterologous enzymes into the reaction chambers of fungal fatty acid synthases (FASs) demonstrates the capacity of these megaenzymes for engineered production of short- and medium-chain fatty acids and methyl ketones.

    • Zhiwei Zhu
    • , Yongjin J Zhou
    • , Anastasia Krivoruchko
    • , Martin Grininger
    • , Zongbao K Zhao
    •  & Jens Nielsen
  • Brief Communication |

    Pharmacological chaperones improve folding of destabilized Escherichia coli dihydrofolate reductase (DHFR) and human disease-linked α-galactosidase A (α-GAL) by biasing the kinetic partitioning between folding, aggregation, and degradation. Chaperoning spares DHFR from aggregation and α-GAL from degradation.

    • Karan S Hingorani
    • , Matthew C Metcalf
    • , Derrick T Deming
    • , Scott C Garman
    • , Evan T Powers
    •  & Lila M Gierasch
  • Brief Communication |

    In vitro and in silico analysis enables the rational design of fatty acid synthase (FAS)-mediated pathways for the compartmentalized production of desirable fatty acids and a polyketide lactone.

    • Jan Gajewski
    • , Floris Buelens
    • , Sascha Serdjukow
    • , Melanie Janßen
    • , Niña Cortina
    • , Helmut Grubmüller
    •  & Martin Grininger
  • Brief Communication |

    Discovery and characterization of an unusually permissive C-prenyltransferase provides a biocatalytic route for generating novel prenylated compounds, including daptomycin derivatives with increased potency.

    • Sherif I Elshahawi
    • , Hongnan Cao
    • , Khaled A Shaaban
    • , Larissa V Ponomareva
    • , Thangaiah Subramanian
    • , Mark L Farman
    • , H Peter Spielmann
    • , George N Phillips Jr
    • , Jon S Thorson
    •  & Shanteri Singh
  • Brief Communication |

    A structural study of MraY, an essential enzyme from Clostridium bolteae involved in bacterial cell wall synthesis, in complex with the natural product antibiotic tunicamycin, provides a basis for future antibiotic design.

    • Jonna K Hakulinen
    • , Jenny Hering
    • , Gisela Brändén
    • , Hongming Chen
    • , Arjan Snijder
    • , Margareta Ek
    •  & Patrik Johansson
  • Brief Communication |

    The combination of an extremely soluble chimeric spider silk protein (spidroin) and a biomimetic spinning method that recapitulates the endogenous pH gradient in silk glands produces a remarkably strong artificial spider silk.

    • Marlene Andersson
    • , Qiupin Jia
    • , Ana Abella
    • , Xiau-Yeen Lee
    • , Michael Landreh
    • , Pasi Purhonen
    • , Hans Hebert
    • , Maria Tenje
    • , Carol V Robinson
    • , Qing Meng
    • , Gustavo R Plaza
    • , Jan Johansson
    •  & Anna Rising
  • Brief Communication |

    The synergistic effect of the GPCR β2AR on signaling through another GPCR, PTHR, is explained by the release of Gβγ from the heterotrimeric Gαiβγ protein, activating adenylate cyclase AC2 and subsequent prolonged cAMP signaling in internal compartments

    • Frédéric G Jean-Alphonse
    • , Vanessa L Wehbi
    • , Jingming Chen
    • , Masaki Noda
    • , Juan M Taboas
    • , Kunhong Xiao
    •  & Jean-Pierre Vilardaga
  • Brief Communication |

    The development of small-molecule fluorescent probes through addition of a lipidated cysteine residue next to a caged fluorophore enables detection of endogenous cysteine depalmitoylation by acyl–protein thioesterases in vitro and in live cells.

    • Rahul S Kathayat
    • , Pablo D Elvira
    •  & Bryan C Dickinson
  • Brief Communication |

    The iron protein components of bacterial nitrogenases are capable of reducing carbon dioxide (CO2) to carbon monoxide (CO) in the absence of their catalytic partners, mimicking the activity of CO dehydrogenase.

    • Johannes G Rebelein
    • , Martin T Stiebritz
    • , Chi Chung Lee
    •  & Yilin Hu