Molecular biophysics

  • Article
    | Open Access

    A method that uses a combination of optical trapping, fluorescence microscopy and microfluidics to analyse the internal structure of chromosomes shows that there is a distinct nonlinear stiffening of the chromosome in response to tension.

    • Anna E. C. Meijering
    • , Kata Sarlós
    •  & Gijs J. L. Wuite
  • Article |

    A high-throughput, chromosome-wide analysis of DNA looping reveals its contribution to the organization of chromatin, and provides insight into how nucleosomes are deposited and organised de novo.

    • Aakash Basu
    • , Dmitriy G. Bobrovnikov
    •  & Taekjip Ha
  • Article |

    Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.

    • Emil Marklund
    • , Brad van Oosten
    •  & Sebastian Deindl
  • Article |

    The cryo-electron microscopy structure of the yeast SWI/SNF complex bound to a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes and suggests mechanisms by which the mutated proteins may cause cancer.

    • Yan Han
    • , Alexis A Reyes
    •  & Yuan He
  • Article |

    Single-molecule visualization shows that condensin—a motor protein that extrudes DNA in one direction only—can encounter and pass a second condensin molecule to form a new type of DNA loop that gathers DNA from both sides.

    • Eugene Kim
    • , Jacob Kerssemakers
    •  & Cees Dekker
  • Article |

    Cryo-electron microscopy and high-speed atomic force microscopy reveal that PIEZO1 can reversibly deform its shape towards a planar structure, which may explain how the PIEZO1 channel is gated in response to mechanical stimulation.

    • Yi-Chih Lin
    • , Yusong R. Guo
    •  & Simon Scheuring
  • Letter |

    ORBIT (origami-rotor-based imaging and tracking) is used to track the DNA rotation that results from DNA unwinding by RecBCD helicase and transcription by RNAP at a single-molecule scale and millisecond time resolution.

    • Pallav Kosuri
    • , Benjamin D. Altheimer
    •  & Xiaowei Zhuang
  • Letter |

    By engineering entropy-tuning changes into distal sites of a bacterial adenylate kinase, an allosteric tuning mechanism based on protein dynamics is revealed.

    • Harry G. Saavedra
    • , James O. Wrabl
    •  & Vincent J. Hilser
  • Letter |

    Cryo-electron microscopy structures of two stoichiometries of heteromeric acetylcholine receptors in complex with nicotine reveal principles of subunit assembly and the structural basis of the distinctive biophysical and pharmacological properties of the different stoichiometries.

    • Richard M. Walsh Jr
    • , Soung-Hun Roh
    •  & Ryan E. Hibbs
  • Letter |

    Molecular dynamics simulations and site-directed fluorescence spectroscopy show that the transmembrane core and cytoplasmic tail of G-protein-coupled receptors independently and cooperatively activate arrestin.

    • Naomi R. Latorraca
    • , Jason K. Wang
    •  & Ron O. Dror
  • Letter |

    The cryo-electron microscopy structure of the ten-subunit human transcription factor IIH, revealing the molecular architecture of the TFIIH core complex, the detailed structures of its constituent XPB and XPD ATPases, and how the core and kinase subcomplexes of TFIIH are connected.

    • Basil J. Greber
    • , Thi Hoang Duong Nguyen
    •  & Eva Nogales
  • Analysis |

    The large number of small, similarly sized proteins and the small number of heavy RNA molecules that make up a ribosome reduce the time required for reproduction.

    • Shlomi Reuveni
    • , Måns Ehrenberg
    •  & Johan Paulsson
  • Article |

    Single-molecule FRET imaging provides insights into the allosteric link between the ligand-binding and G-protein nucleotide-binding pockets of the β2 adrenergic receptor (β2AR) and improved understanding of the G-protein activation mechanism.

    • G. Glenn Gregorio
    • , Matthieu Masureel
    •  & Scott C. Blanchard
  • Letter |

    The near-complete in vitro reconstitution of the mitotic spindle assembly checkpoint reveals how the assembly of its effector, the mitotic checkpoint complex, is catalysed.

    • Alex C. Faesen
    • , Maria Thanasoula
    •  & Andrea Musacchio
  • Article |

    Cryo-electron microscopy structural models of the human pre-initiation complex at all major steps of transcription initiation at near atomic-level resolution are presented, providing new mechanistic insights into the processes of promoter melting and transcription-bubble formation, as well as an almost complete proposed structural model of all of the pre-initiation complex components and their interactions with DNA.

    • Yuan He
    • , Chunli Yan
    •  & Eva Nogales
  • Article |

    The cryo-electron microscopy structures of yeast initiation complexes containing the transcription factors TBP, TFIIA, TFIIB, TFIIE, and TFIIF and containing either closed or open promoter DNA are reported, providing mechanistic insights into DNA opening and template-strand loading.

    • C. Plaschka
    • , M. Hantsche
    •  & P. Cramer
  • Article |

    dG•dT and rG•rU ‘wobble’ mispairs in DNA and RNA transiently form base pairs with Watson–Crick geometry via tautomerization and ionization with probabilities that correlate with misincorporation probabilities during replication and translation.

    • Isaac J. Kimsey
    • , Katja Petzold
    •  & Hashim M. Al-Hashimi
  • Letter |

    This study shows how the yeast Ctf4 protein couples the DNA helicase, Cdc45–MCM–GINS, to DNA polymerase α — the GINS subunit of the helicase and the polymerase use a similar interaction to bind Ctf4, suggesting that, as Ctf4 is a trimer, two polymerases could be simultaneously coupled to a single helicase during lagging-strand synthesis.

    • Aline C. Simon
    • , Jin C. Zhou
    •  & Luca Pellegrini
  • Letter |

    The solution and crystal structures of a bacterial phytochrome photosensory core in both its resting and activated states are determined; switching between closed (resting) and open (activated) forms is found to be mediated by a conserved ‘tongue’, and the structures indicate that smaller changes in the vicinity of the chromophore are amplified in scale as they are transmitted through the tongue and beyond.

    • Heikki Takala
    • , Alexander Björling
    •  & Sebastian Westenhoff
  • Letter |

    The co-crystal structure of the T-box tRNA-binding region, stem I, bound to tRNA is solved, showing that this region not only binds the anticodon, but also cradles the entire tRNA, forming an extended interface; the two T-loop motifs of stem I mediate interactions similar to those of RNase P and the large ribosomal subunit, even though the three species do not share a common evolutionary ancestor.

    • Jinwei Zhang
    •  & Adrian R. Ferré-D’Amaré
  • Letter |

    A human lipid transfer protein (GLTPD1, named here CPTP) is shown to regulate eicosanoid production by mediating the intermembrane transfer of the phosphorylated sphingolipid ceramide-1-phosphate through a non-vesicular transport mechanism elucidated by structural, functional and biological data.

    • Dhirendra K. Simanshu
    • , Ravi Kanth Kamlekar
    •  & Dinshaw J. Patel
  • Letter |

    The bacterial RecBCD helicase/nuclease shows broad, and apparently static, heterogeneity in the unwinding rate manifest by individual molecules: here it is shown that transiently halting an enzyme during processive translocation allows for a change, most likely conformational, such that the velocity of the molecule after pausing can fall anywhere within the spectrum of rates seen for a population.

    • Bian Liu
    • , Ronald J. Baskin
    •  & Stephen C. Kowalczykowski
  • Letter |

    In the human pathogen Vibrio vulnificus, the riboswitch regulating gene expression of the adenosine deaminase is shown to exist in three distinct stable conformational states; this three-state mechanism allows control of gene expression over a broad temperature range, which is essential for Vibrio adaptation.

    • Anke Reining
    • , Senada Nozinovic
    •  & Harald Schwalbe
  • Article |

    This study develops an NMR-based approach that can capture previously inaccessible, highly transient, low-populated ‘excited states’ in RNA; the localized rearrangements in base-pairing giving rise to these states are found to affect function by changing the exposure of residues required for a specific biological process.

    • Elizabeth A. Dethoff
    • , Katja Petzold
    •  & Hashim M. Al-Hashimi
  • Article |

    After introducing the T-cell receptor and other essential signalling genes, a non-immune cell is capable of displaying the early events of T-cell activation when placed in contact with antigen-presenting cells, and the initial signalling in this reconstituted system is shown to require the spatial reorganization of molecules at the cell interface.

    • John R. James
    •  & Ronald D. Vale
  • Letter |

    Stalled bacterial ribosomes can be rescued by interaction with SmpB protein and a highly structured transfer-messenger RNA, and a cryo-electron microscopy map of this complex now shows how EF-G-dependent translocation of this non-canonical ligand is facilitated by conformational changes in the ribosome and the transfer-messenger RNA.

    • David J. F. Ramrath
    • , Hiroshi Yamamoto
    •  & Christian M. T. Spahn
  • Article |

    Genetically encoded neural activity markers were used in mice to simultaneously follow large populations of motor cortex neurons during sensorimotor learning, revealing that spatially intermingled neurons represent either sensory or motor behaviour, with population-level representations of subsets of motor programs strengthening as training progressed.

    • D. Huber
    • , D. A. Gutnisky
    •  & K. Svoboda
  • Letter |

    A functional electrical stimulation system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain can be used to control the intensity of stimulation of muscles that are temporarily paralysed by pharmacological motor nerve blockade, thereby restoring voluntary control of the affected muscles; this is a major advance towards similar restoration of hand function in human patients with spinal cord injury.

    • C. Ethier
    • , E. R. Oby
    •  & L. E. Miller