Biochemistry articles within Nature

Featured

  • Article |

    The γ-carboxylation of many blood coagulation factors relies on the generation of vitamin K hydroquinone by the enzyme vitamin K epoxide reductase (VKOR), of which the anticoagulant warfarin is an inhibitor. Here, the X-ray crystal structure of a bacterial homologue of VKOR is presented; the results have implications for the mechanism of action of mammalian VKOR and explain how mutations can cause warfarin resistance.

    • Weikai Li
    • , Sol Schulman
    •  & Tom A. Rapoport
  • Article |

    Mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. Here, mature differentiated cells are directed, via a combination of a few transcription factors (distinct from those described for generating iPS cells), to form functional neurons in vitro, without having to revert the fibroblasts to an embryonic state.

    • Thomas Vierbuchen
    • , Austin Ostermeier
    •  & Marius Wernig
  • Letter |

    The extent of epigenetic reprogramming in mammalian primordial germ cells (PGCs) and in early embryos, and its molecular mechanisms, are poorly understood. DNA methylation profiling in PGCs now reveals a genome–wide erasure of methylation, with female PGCs being less methylated than male ones. A deficiency of the cytidine deaminase AID interferes with the genome–wide erasure of DNA methylation, indicating that AID has a critical function in epigenetic reprogramming.

    • Christian Popp
    • , Wendy Dean
    •  & Wolf Reik
  • Brief Communications Arising |

    • Sophie Brinster
    • , Gilles Lamberet
    •  & Claire Poyart
  • Letter |

    Although cyclin D1 is frequently overexpressed in human cancers, the full range of its functions in normal development and oncogenesis is unclear. Here, tagged cyclin D1 knock-in mouse strains are developed to allow a search for cyclin D1-binding proteins in different mouse organs using high-throughput mass spectrometry. The results show that, in addition to its established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development.

    • Frédéric Bienvenu
    • , Siwanon Jirawatnotai
    •  & Piotr Sicinski
  • Letter |

    Antimicrobial peptides (AMPs) are an important class of immune effector molecules which fight pathogen infections. AMP induction in Drosophila is regulated through the activation of the Toll and immune deficiency pathways; it is now shown that AMP activation can be achieved independently of these pathways by the transcription factor FOXO. In non-infected animals, AMP genes are activated in response to nuclear FOXO activity when induced by starvation.

    • Thomas Becker
    • , Gerrit Loch
    •  & Michael Hoch
  • Letter |

    Group II chaperonins are present in eukaryotes and archaea and are essential mediators of cellular protein folding. This process is critically dependent on the closure of a built-in lid, which is triggered by ATP hydrolysis, but the structural rearrangements and molecular events leading to lid closure are unknown. Using cryo-electron microscopy, the structures of an archaeal group II chaperonin in the open and closed states are now reported, providing details of this mechanism.

    • Junjie Zhang
    • , Matthew L. Baker
    •  & Wah Chiu
  • Authors |

    Testosterone's 'bad guy' image is rooted in folklore, not fact.

  • Letter |

    The amino acid antiporter AdiC is important for the survival of enteric bacteria such as Escherichia coli in extremely acid environments. Although the structure of substrate-free AdiC is known, how the substrate (arginine or agmatine) is recognized and transported by AdiC remains unclear. The crystal structure of an E. coli AdiC variant bound to arginine is now reported and analysed.

    • Xiang Gao
    • , Lijun Zhou
    •  & Yigong Shi
  • Article |

    Form I Rubisco, one of the most abundant proteins in nature, catalyses the fixation of atmospheric CO2 in photosynthesis. The limited catalytic efficiency of Rubisco has sparked extensive efforts to re-engineer the enzyme to enhance agricultural productivity. To bring this goal closer, the formation of cyanobacterial form I Rubisco is now analysed by in vitro reconstitution and cryo-electron microscopy.

    • Cuimin Liu
    • , Anna L. Young
    •  & Manajit Hayer-Hartl
  • Letter |

    Rho is a general transcription termination factor in bacteria, but the mechanism by which it disrupts the RNA polymerase (RNAP) elongation complex is unknown. Here, Rho is shown to bind tightly to the RNAP throughout the transcription cycle, with the formation of the RNAP–Rho complex being crucial for termination. Furthermore, RNAP is proposed to have an active role in Rho termination through an allosteric mechanism.

    • Vitaly Epshtein
    • , Dipak Dutta
    •  & Evgeny Nudler
  • Letter |

    Phytochromes regulate numerous photoresponses in plants and microorganisms through their ability to photointerconvert between a red-light-absorbing, ground state (Pf) and a far-red-light-absorbing, photoactivated state (Pfr). The structures of several phytochromes as Pf have been determined previously; here, the three-dimensional solution structure of the bilin-binding domain as Pfr is described. The results shed light on the structural basis for photoconversion to the activated Pfr form.

    • Andrew T. Ulijasz
    • , Gabriel Cornilescu
    •  & Richard D. Vierstra
  • News & Views |

    Chemical models of enzymes' active sites aid our understanding of biological reactions. Such a model of a reaction intermediate promises to advance our knowledge of the biochemistry of iron-containing haem enzymes.

    • Kenneth D. Karlin
  • News & Views |

    The key enzyme in photosynthesis, Rubisco, is a relic of a bygone age. The ability to assemble Rubisco in the test tube offers the prospect of genetically manipulating the enzyme to make it fit for the modern world.

    • R. John Ellis
  • News & Views |

    Memory formation is known to occur at the level of synaptic contacts between neurons. It therefore comes as a surprise that another type of brain cell, the astrocyte, is also involved in establishing memory.

    • Mirko Santello
    •  & Andrea Volterra
  • Letter |

    Distinguishing self from non-self is a vital function for immune systems to repel invaders without inducing autoimmunity. One system, which protects bacteria and archaea from invasion by phage and plasmid DNA, involves clustered, regularly interspaced, short palindromic repeat (CRISPR) loci. Here, in Staphylococcus epidermidis, the mechanism of CRISPR self/non-self discrimination is defined.

    • Luciano A. Marraffini
    •  & Erik J. Sontheimer
  • Article |

    GNF-2 is a recently discovered, selective allosteric Bcr–Abl inhibitor. Solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry are now used to show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. The results show that the combination of allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.

    • Jianming Zhang
    • , Francisco J. Adrián
    •  & Nathanael S. Gray
  • Letter |

    Phenotypic robustness in the face of genetic and environmental perturbations — known as canalization — relies on buffering mechanisms. Hsp90 chaperone machinery has been proposed to be an evolutionarily conserved buffering mechanism of phenotypic variance. Here, an additional, perhaps alternative, mechanism whereby Hsp90 influences phenotypic variation is proposed; Hsp90 mutations can generate new variation by transposon-mediated mutagenesis.

    • Valeria Specchia
    • , Lucia Piacentini
    •  & Maria P. Bozzetti
  • Letter |

    If the activity of genetically specified neurons is silenced in a temporally precise fashion, the roles of different cell classes in neural processes can be studied. Members of the class of light-driven outward proton pumps are now shown to mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) enables near 100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light.

    • Brian Y. Chow
    • , Xue Han
    •  & Edward S. Boyden
  • Article |

    Although Archaea encode proteasomes highly related to those of eukaryotes, archaeal ubiquitin-like proteins are less conserved and not known to function in protein conjugation, complicating our understanding of the origins of ubiquitination. Two small archaeal modifier proteins, SAMP1 and SAMP2, structurally similar to ubiquitin, are now reported to form protein conjugates in the archaeon Haloferax volcanii.

    • Matthew A. Humbard
    • , Hugo V. Miranda
    •  & Julie A. Maupin-Furlow
  • Letter |

    G-protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters and are the largest group of therapeutic targets for a range of diseases. The extracellular surface (ECS) of GPCRs is diverse and therefore an ideal target for the discovery of subtype-selective drugs. Here, NMR spectroscopy is used to investigate ligand-specific conformational changes around a central structural feature in the ECS of a GPCR.

    • Michael P. Bokoch
    • , Yaozhong Zou
    •  & Brian K. Kobilka