Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    Prion protein has been suggested to bind toxic amyloid-ß oligomers. Nicollet al.demonstrate that binding to prion protein and prion protein-dependent synaptotoxicity correlate with the presence of a tubular form of amyloid-ß with a defined triple helical structure.

    • Andrew J. Nicoll
    • , Silvia Panico
    •  & John Collinge
  • Article
    | Open Access

    The helicases UvsW and RecG have both unwinding and rewinding activities and are involved in the rescue of stalled DNA replication forks. Here Manosas et al. use single-molecule techniques to characterize the rewinding activities of the two helicases, concluding that rewinding is actively catalysed.

    • Maria Manosas
    • , Senthil K. Perumal
    •  & Vincent Croquette
  • Article |

    Protein deacetylases of the sirtuin family have important roles in aging and metabolism. Using peptide microarrays displaying physiological lysine acetylation sites, the authors map the substrate preferences of all seven human sirtuin isoforms, revealing enzyme specificities and identifying new sirtuin substrates.

    • David Rauh
    • , Frank Fischer
    •  & Clemens Steegborn
  • Article |

    TMEM16-channel family members have been shown to be involved in Ca2+-dependent lipid scrambling, but whether they have intrinsic scramblase activity remains controversial. Malvezzi et al. identify a TMEM16 family member in Aspergillus in which a single Ca2+-binding site regulates intrinsic channel and scramblase activities.

    • Mattia Malvezzi
    • , Madhavan Chalat
    •  & Alessio Accardi
  • Article |

    The ability to induce metabolic pathways in response to a changing environment is an important component of bacterial fitness. Bartl et al. identify optimal programmes for metabolic pathway activation depending on protein synthesis capacity constraints, and demonstrate their impact on operonic organization.

    • Martin Bartl
    • , Martin Kötzing
    •  & Christoph Kaleta
  • Article
    | Open Access

    Components of the complement system have been shown to promote liver regeneration. Haynes et al. demonstrate that the complement fragment C3a can induce regeneration of the embryonic chick retina from stem and progenitor cells of the ciliary margin via activation of STAT3 and other downstream signalling pathways.

    • Tracy Haynes
    • , Agustin Luz-Madrigal
    •  & Katia Del Rio-Tsonis
  • Article |

    Srs2 is a DNA helicase and single-stranded DNA translocase that prevents homologous recombination by dismantling Rad51 filaments. Qiu et al.use single-molecule techniques to describe Rad51 filament formation and show that Srs2 displays repetitive activity on single-stranded DNA, which prevents re-formation of Rad51 filaments after dismantling.

    • Yupeng Qiu
    • , Edwin Antony
    •  & Sua Myong
  • Article
    | Open Access

    Poly-ADP-ribosylation is a post-translational modification that is countered by poly(ADP-ribose) glycohydrolases (PARGs). In this study, the authors present the crystal structure of poly(ADP-ribose) glycohydrolase (PARGs) in complex with a poly(ADP-ribose) substrate, and reveal that poly(ADP-ribose) glycohydrolase (PARGs) enzymes act predominantly as exo- rather than as endo-glycohydrolases.

    • Eva Barkauskaite
    • , Amy Brassington
    •  & David Leys
  • Article
    | Open Access

    Bacterial endonuclease V enzymes are characterized as DNA repair proteins. Here the authors show that human endonuclease V is an inosine-specific ribonuclease, indicating a role for this enzyme in normal RNA metabolism rather than DNA repair.

    • Erik Sebastian Vik
    • , Meh Sameen Nawaz
    •  & Ingrun Alseth
  • Article
    | Open Access

    In Escherichia coli, the highly conserved enzyme endonuclease V has a role in DNA repair. Here the authors show that human endonuclease V is an inosine 3' endoribonuclease and that Tudor Staphylococcal nuclease enhances this activity, suggesting a role for human endonuclease V in RNA metabolism.

    • Yoko Morita
    • , Toshihiro Shibutani
    •  & Isao Kuraoka
  • Article |

    Clinical trials of γ-secretase inhibitors to treat Alzheimer’s disease show that side effects occur from their non-selective action. Dimitrov et al.show that improved second generation γ-secretase modulators spare cleavage sites of substrate proteins that are implicated in the side effects.

    • Mitko Dimitrov
    • , Jean-René Alattia
    •  & Patrick C. Fraering
  • Article |

    A central, imperfect duplex RNA secondary structure is generally required for site-specific adenosine-to-inosine RNA editing by ADAR enzymes. Rieder et al. show in Drosophila that conserved and complex long-range RNA tertiary structures form in vivoand can also regulate specific RNA-editing events by ADAR enzymes.

    • Leila E. Rieder
    • , Cynthia J. Staber
    •  & Robert A. Reenan
  • Article |

    The 26S proteasome comprises over 33 different subunits that must be correctly assembled by dedicated chaperones for efficient protein degradation. Here the authors find that general chaperone proteins are also vital for proper proteasome assembly.

    • Takashi Akahane
    • , Kazutaka Sahara
    •  & Shigeo Murata
  • Article
    | Open Access

    Many patients with breast cancer develop resistance to the drug tamoxifen and relapse. Here Johansson et al. identify the nuclear receptor retinoic acid receptor alpha (RARA) as a marker of tamoxifen resistance and show that RARA expression correlates negatively with relapse-free survival of patients.

    • Henrik J. Johansson
    • , Betzabe C. Sanchez
    •  & Janne Lehtiö
  • Article |

    The complexity and dynamic range of mammalian proteomes has stymied comprehensive protein quantification for the past twenty years. Zhou et al. develop DEEP SEQ mass spectrometry and use it to quantify a murine stem cell proteome to a depth equivalent to RNA-seq-based ribosome profiling.

    • Feng Zhou
    • , Yu Lu
    •  & Jarrod A. Marto
  • Article
    | Open Access

    The malaria parasite Plasmodium falciparum utilizes thiamine for the production of essential enzymatic cofactors. Chan et al. show that inhibition of thiamine utilization with oxythiamine inhibits proliferation of P. falciparumand reduces parasite growth in a mouse model of malaria infection.

    • Xie Wah Audrey Chan
    • , Carsten Wrenger
    •  & Kevin J. Saliba
  • Article
    | Open Access

    RamR is an important multidrug-resistance factor, however, its structure and the molecules to which it responds are hitherto unknown. Here, the authors report the crystal structures of RamR complexed with multiple drugs, revealing significant flexibility in its substrate-recognition region.

    • Suguru Yamasaki
    • , Eiji Nikaido
    •  & Kunihiko Nishino
  • Article
    | Open Access

    Mutations in the E3 ubiquitin ligase parkin are associated with juvenile Parkinson’s disease. Here the authors report the solution structure of the Parkin RING2 domain, revealing how disease-associated mutations affect its function and providing a molecular explanation for the recessive nature of the disease.

    • Donald E. Spratt
    • , R Julio Martinez-Torres
    •  & Gary S. Shaw
  • Article
    | Open Access

    The switch from linear to cyclic electron flow has long been thought to rely on the migration of antenna proteins from Photosystem II to Photosystem I. Takahashi et al. report that this is not the case and that cyclic electron flow is tuned by the intrachloroplastic redox power.

    • Hiroko Takahashi
    • , Sophie Clowez
    •  & Fabrice Rappaport
  • Article
    | Open Access

    Voltage-gated potassium channels open and close in response to changes in transmembrane potential, but their opening mechanism is poorly understood. Here, free energy molecular dynamics simulations show that strain accumulates as the pore closes, which subsequently drives opening.

    • Philip W. Fowler
    •  & Mark S. P. Sansom
  • Article |

    Light-sensitive proteins are useful tools to control protein localization and gene expression, but are currently limited to excitation with red or blue light. Here Crefcoeur et al. present a novel optogenetic system to induce protein–protein interactions with ultraviolet-B light that does not require exogenous chromophores.

    • Remco P. Crefcoeur
    • , Ruohe Yin
    •  & Thanos D. Halazonetis
  • Article
    | Open Access

    Single-molecule force spectroscopy provides useful quantitative information about the properties of macromolecules. Otto and colleagues non-invasively inspect the tension dynamics in a taut strand of DNA, thereby extending the use of single-molecule force spectroscopy to the study of macromolecular dynamics.

    • Oliver Otto
    • , Sebastian Sturm
    •  & Klaus Kroy
  • Article |

    Guanine-rich DNA can form four-stranded structures called G-quadruplexes, which are thought to influence DNA replication, transcription and repair; their stability and prevalence in the genome is in need of further elucidation. Here the authors employ an antibody-based approach to sensitively map G-quadruplexes in the genome.

    • Enid Yi Ni Lam
    • , Dario Beraldi
    •  & Shankar Balasubramanian
  • Article
    | Open Access

    Voltage-gated potassium channels cycle between closed and open states through poorly-defined transitions. Pless and colleagues incorporate artificial amino acids into Shaker potassium channels and find that that the negative electrostatic surface potential of Phe481, destabilizes the channel open state.

    • Stephan A. Pless
    • , Ana P. Niciforovic
    •  & Christopher A. Ahern
  • Article
    | Open Access

    Mutations of the SOD1gene are implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis. Wright and colleagues find that SOD1 aggregation in cells is arrested by compounds that bind at the core of SOD1 aggregates, rather than at the dimer interface site.

    • Gareth S.A. Wright
    • , Svetlana V. Antonyuk
    •  & S Samar Hasnain
  • Article
    | Open Access

    IP39 is an abundant protozoan protein known to form highly-ordered striations in Euglena gracilis’ plasma membrane. Here, Suzuki et al. determine its three-dimensional structure by electron crystallography revealing that IP39 polymerises to form trimeric longitudinal units arranged in a molecular strand of antiparallel double-rows.

    • Hiroshi Suzuki
    • , Yasuyuki Ito
    •  & Sachiko Tsukita
  • Article |

    Dynamin promotes membrane fission by constricting the neck of invaginating membranes; however, it was recently shown that dynamin also regulates membrane fusion. Here the authors show that this fusogenic activity is mediated by interaction with the Qa SNARE, thereby promoting trans-SNARE formation.

    • Kannan Alpadi
    • , Aditya Kulkarni
    •  & Christopher Peters
  • Article |

    Alcohols and anaesthetics exert their effects by potentiating ligand-gated ion channels. Here, the authors determine crystal structures of a bacterial ligand-gated ion channel in the presence of alcohols and anaesthetics, and describe a structural mechanism for stabilization of the open form of the channel.

    • Ludovic Sauguet
    • , Rebecca J. Howard
    •  & Marc Delarue
  • Article
    | Open Access

    The protein α4 is essential for the formation, stability and activity of protein phosphatase 2A (PP2A) complexes. Here the authors solve the crystal structure of a truncated PP2A bound to α4 and show that α4 binds to a partially folded form of the protein, stabilizing the enzyme in an inactive state.

    • Li Jiang
    • , Vitali Stanevich
    •  & Yongna Xing
  • Article |

    Ribosomal protein synthesis is driven by the hydrolysis of GTP. Wallin and colleagues employ molecular dynamics and computer simulations to show that a universally conserved histidine promotes GTP hydrolysis in its protonated form, and is driven into the active conformation by interactions with the ribosome.

    • Göran Wallin
    • , Shina C. L. Kamerlin
    •  & Johan Åqvist
  • Article |

    RecA/Rad51 proteins catalyse the recognition and exchange between two homologous DNA strands during homologous recombination. Sasanuma et al. now demonstrate that Rad51 association with ssDNA is mediated by a complex consisting of Psy3, Csm2, Shu1 and Shu2 proteins.

    • Hiroyuki Sasanuma
    • , Maki S. Tawaramoto
    •  & Akira Shinohara