Biochemistry

  • Article
    | Open Access

    Structural insights into the poly-ADP-ribosyltransferase tankyrase reveal its filamentous architecture and illustrate how assembly controls catalytic and non-catalytic functions.

    • Nisha Pillay
    • , Laura Mariotti
    •  & Sebastian Guettler
  • Article |

    Electrophysiological, structural and biochemical studies on the bestrophin-2 anion channel reveal asymmetric permeability to glutamate and show that it forms a cooperative machinery in complex with glutamine synthetase for glutamate release.

    • Aaron P. Owji
    • , Kuai Yu
    •  & Tingting Yang
  • Article
    | Open Access

    Cryo-electron microscopy structures of skeletal F-actin show solvent-driven rearrangements governing actin filament assembly and aging with potential application in design of drugs and small molecules for imaging and therapy.

    • Wout Oosterheert
    • , Björn U. Klink
    •  & Stefan Raunser
  • Article
    | Open Access

    The cryo-EM structure of the yeast SEA complex suggests that SEACAT functions as a scaffold for binding TORC1 regulators.

    • Lucas Tafur
    • , Kerstin Hinterndorfer
    •  & Robbie Loewith
  • Article |

    Two cyclic dinucleotide molecules bind within the cavity of human SLC19A1 as a compact dual-molecule unit, whereas folate and antifolate bind to SLC19A1 as a monomer and occupy a distinct pocket of the cavity.

    • Qixiang Zhang
    • , Xuyuan Zhang
    •  & Pu Gao
  • Article |

    Biochemical and structural analysis of intermediates during multipass membrane protein biogenesis showed how an intramembrane chaperone guides nascent membrane proteins to a semi-enclosed lipid-filled cavity where they are inserted and folded correctly.

    • Luka Smalinskaitė
    • , Min Kyung Kim
    •  & Ramanujan S. Hegde
  • Article
    | Open Access

    The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.

    • Seiichi Hirano
    • , Kalli Kappel
    •  & Feng Zhang
  • Article |

    NMR spectroscopy has been used to guide the directed evolution of myoglobin to a Kemp eliminase with high catalytic efficiency, outlining an approach that is likely to be generally applicable to other enzyme activities.

    • Sagar Bhattacharya
    • , Eleonora G. Margheritis
    •  & Ivan V. Korendovych
  • Article
    | Open Access

    Cryo-electron tomography is used to reveal the structural dynamics and functional diversity of translating ribosomes in Mycoplasma pneumoniae, providing insight into the translation elongation cycle inside cells and how it is reshaped by antibiotics.

    • Liang Xue
    • , Swantje Lenz
    •  & Julia Mahamid
  • Article |

    A structural analysis focusing on plant immunity reveals how LRR-containing receptor-like proteins recognize pathogenic ligands and consequently become activated, with the data suggesting that these proteins target pathogens through two different mechanisms.

    • Yue Sun
    • , Yan Wang
    •  & Jijie Chai
  • Article |

    A genetically encoded triplet photosensitizer is used to develop an efficient photoenzyme that can promote enantioselective intramolecular and bimolecular [2+2] cycloadditions by means of triplet energy transfer.

    • Jonathan S. Trimble
    • , Rebecca Crawshaw
    •  & Anthony P. Green
  • Article |

    Cryo-electron microscopy studies of Escherichia coli complex I suggest a conserved mechanism of coupled proton transfers and electrostatic interactions that result in proton ejection from the complex exclusively at the distal NuoL subunit.

    • Vladyslav Kravchuk
    • , Olga Petrova
    •  & Leonid Sazanov
  • Article |

    A bacterial antiviral defence system generates a cyclic tri-adenylate that binds to a TIR–SAVED effector, inducing formation of a superhelical structure with adjacent TIR domains organizing into an active site, allowing NAD+ degradation.

    • Gaëlle Hogrel
    • , Abbie Guild
    •  & Malcolm F. White
  • Article
    | Open Access

    Reconstitution of the SARS-CoV-2 RNA 5′ cap reveals the unconventional mechanism by which SARS-CoV-2 caps its RNA genome, providing a new target in the development of antiviral agents to treat COVID-19.

    • Gina J. Park
    • , Adam Osinski
    •  & Vincent S. Tagliabracci
  • Article |

    Thyroid-stimulating hormone and autoantibody M22 push the extracellular domain of the thyrotropin receptor into an upright active conformation, revealing a universal activation mechanism of glycoprotein hormone receptors and providing the molecular basis of Graves’ disease, hypothyroidism and Hashimoto’s disease.

    • Jia Duan
    • , Peiyu Xu
    •  & H. Eric Xu
  • Article
    | Open Access

    Biochemical and lipidomic analyses identify an anti-ferroptotic function of vitamin K and reveal ferroptosis suppressor protein 1 (FSP1) as the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle.

    • Eikan Mishima
    • , Junya Ito
    •  & Marcus Conrad
  • Article |

    Inhibiting the asialoglycoprotein receptor ASGR1 increases cholesterol excretion to the bile and then faeces, providing a unique way to lower cholesterol, and therefore providing a safe and effective way to treat cardiovascular disease.

    • Ju-Qiong Wang
    • , Liang-Liang Li
    •  & Bao-Liang Song
  • Article
    | Open Access

    Systematic measurements of the interactions between proteins found on the surfaces of human leukocytes provides a global view of the way that immune cells are dynamically connected by receptors.

    • Jarrod Shilts
    • , Yannik Severin
    •  & Gavin J. Wright
  • Article
    | Open Access

    Structures of the Arabidopsis thaliana auxin exporter PIN1 in the apo state, bound to the natural auxin or bound to an inhibitor provide insights into the polar auxin transport mechanisms mediated by PIN family transporters.

    • Zhisen Yang
    • , Jing Xia
    •  & Linfeng Sun
  • Article |

    Cryo-electron microscopy structures of the bacterial protein machinery that is involved in the production and function of nitrous oxide provide insight into the assembly pathway of this enzyme and the mechanisms of copper transport.

    • Christoph Müller
    • , Lin Zhang
    •  & Oliver Einsle
  • Article
    | Open Access

    The PI3K–PANK4 axis regulates coenzyme A synthesis, the abundance of acetyl-CoA, and CoA-dependent processes such as lipid metabolism, and these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone and growth-factor-driven or oncogene-driven metabolism and growth.

    • Christian C. Dibble
    • , Samuel A. Barritt
    •  & Alex Toker
  • Article
    | Open Access

    Overall, this study describes the molecular mechanism of a druggable pathway that recapitulates in cellular assays the immunomodulatory effects associated with Akkermansia muciniphila, a prominent member of the gut microbiota.

    • Munhyung Bae
    • , Chelsi D. Cassilly
    •  & Jon Clardy
  • Article
    | Open Access

    Cryo-electron microscopy structures of IL-25–IL-17RB–IL-17RA and IL-17A–IL-17RC–IL-17RA complexes show a tip-to-tip architecture, which is a key organizing principle of the IL-17 receptor family.

    • Steven C. Wilson
    • , Nathanael A. Caveney
    •  & K. Christopher Garcia
  • Article
    | Open Access

    Through structural analysis of the activation of bacterial STING, the molecular basis of STING filament formation and TIR effector domain activation in antiphage signalling is defined.

    • Benjamin R. Morehouse
    • , Matthew C. J. Yip
    •  & Philip J. Kranzusch
  • Article |

    Fruitflies require Sestrin to regulate mTORC1 signalling in response to dietary leucine, survive a diet low in leucine, and control leucine-sensitive physiological characteristics, which establishes Sestrin as a physiologically relevant leucine sensor.

    • Xin Gu
    • , Patrick Jouandin
    •  & David M. Sabatini
  • Article |

    The cryo-electron microscopy structure of the filamentous hydrogen-dependent CO2 reductase (HDCR) enzyme from Thermoanaerobacter kivui, together with enzymatic analysis and in situ cryo-electron tomography, provides insight into the high catalytic activity of HDCR.

    • Helge M. Dietrich
    • , Ricardo D. Righetto
    •  & Jan M. Schuller
  • Article
    | Open Access

    A structure of the MRAS–SHOC2–PP1C complex supports a RAS-driven and multi-molecular model for RAF activation in which individual RAS–GTP molecules recruit RAF–14-3-3 and SHOC2–PP1C to activate the downstream pathway.

    • Zachary J. Hauseman
    • , Michelle Fodor
    •  & Daniel A. King
  • Article
    | Open Access

    The Polα–primase-associated CST complex organizes telomeric C-strand DNA synthesis, and, in combination with telomerase, it carries out complete replication of the single-stranded DNA overhang found at human telomeres.

    • Arthur J. Zaug
    • , Karen J. Goodrich
    •  & Thomas R. Cech
  • Article
    | Open Access

    The biosynthetic pathway of strychnine, brucine and diaboline is described, and the biosynthesis of these complex, pharmacologically active compounds has been successfully recapitulated in Nicotiana benthamiana from an upstream intermediate.

    • Benke Hong
    • , Dagny Grzech
    •  & Sarah E. O’Connor
  • Article
    | Open Access

    The evolutionarily conserved RNA-binding protein GTSF1 and its homologues interact with members of the PIWI class of Argonaute proteins, increasing the efficiency of the RNA-cleaving activity of PIWI proteins, an essential function across the animal kingdom.

    • Amena Arif
    • , Shannon Bailey
    •  & Phillip D. Zamore
  • Article
    | Open Access

    Cryo-electron microscopy structure, molecular dynamics and biochemical analyses of the SHOC2–PP1C–MRAS complex demonstrate the dependence of the complex formation on RAS–GTP and identify the determinants of RAS isoform preference for SHOC2–PP1C and specificity of the complex for RAF dephosphorylation.

    • Nicholas P. D. Liau
    • , Matthew C. Johnson
    •  & Jawahar Sudhamsu
  • Article
    | Open Access

    Structures of the Dcr-2–Loqs-PD complex while it is processing a double-stranded RNA (dsRNA) substrate elucidate the interactions between Dcr-2 and Loqs-PD, and show that Dcr-2 undergoes substantial conformational changes during a dsRNA-processing cycle.

    • Shichen Su
    • , Jia Wang
    •  & Jinbiao Ma