Single-molecule biophysics articles within Nature

Featured

  • Article
    | Open Access

    High-speed molecular tracking is integrated with three-dimensional electron microscopy to map the diffusion distribution and ultrastructure of endoplasmic reticulum-mitochondria contact sites, revealing the ability of high-speed single-molecule imaging to map contact site interface structures and corresponding diffusion landscapes.

    • Christopher J. Obara
    • , Jonathon Nixon-Abell
    •  & Jennifer Lippincott-Schwartz
  • Article |

    As well as being the substrate for the lipopolysaccharide transport protein complex comprising LptA–G, lipopolysaccharide binding to Lpt proteins promotes their assembly into a bridge linking the inner and outer membranes of Gram-negative bacteria.

    • Lisa Törk
    • , Caitlin B. Moffatt
    •  & Daniel Kahne
  • Article |

    High-speed atomic force microscopy single-molecule imaging and cryo-EM analysis discover and reveal the structure of a TRPV3 pentamer, providing evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.

    • Shifra Lansky
    • , John Michael Betancourt
    •  & Simon Scheuring
  • Article |

    Two highly charged disordered human proteins phase-separate into viscous complex coacervates while retaining their rapid conformational dynamics through pico- to nanosecond exchange of short-lived side-chain interactions.

    • Nicola Galvanetto
    • , Miloš T. Ivanović
    •  & Benjamin Schuler
  • Article
    | Open Access

    The authors introduce a single-molecule DNA-barcoding method, resolution enhancement by sequential imaging, that improves the resolution of fluorescence microscopy down to the Ångström scale using off-the-shelf fluorescence microscopy hardware and reagents.

    • Susanne C. M. Reinhardt
    • , Luciano A. Masullo
    •  & Ralf Jungmann
  • Article
    | Open Access

    Using single-molecule imaging, the authors show that Smc5/6 forms DNA loops by extrusion, which establishes DNA loop extrusion as a conserved mechanism among eukaryotic SMC complexes.

    • Biswajit Pradhan
    • , Takaharu Kanno
    •  & Eugene Kim
  • Article
    | Open Access

    The reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower compared with bacteria due to eukaryote-specific structural elements in the human ribosome and in the elongation factor eEF1A.

    • Mikael Holm
    • , S. Kundhavai Natchiar
    •  & Scott C. Blanchard
  • Article
    | Open Access

    A structure–function analysis of cystic fibrosis transmembrane conductance regulator shows its two nucleotide-binding domains dimerize before channel opening, and reveals a mechanism through which conformational changes in the channel regulate chloride conductance.

    • Jesper Levring
    • , Daniel S. Terry
    •  & Jue Chen
  • Article |

    Single-molecule measurements of synaptic vesicles show that V-ATPases do not pump continuously in time but instead stochastically switch between ultralong-lived proton-pumping, inactive and proton-leaky modes.

    • Eleftherios Kosmidis
    • , Christopher G. Shuttle
    •  & Dimitrios Stamou
  • 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

    A nanoscale rotary motor made of DNA origami, driven by ratcheting and powered by an external electric field, shows the ability to wind up a spring and has mechanical capabilities approaching those of biological motors.

    • Anna-Katharina Pumm
    • , Wouter Engelen
    •  & Hendrik Dietz
  • Article |

    Single-molecule spectroscopy and structural studies were used to examine the dynamics of association of eIF1A and eIF5B with the human translation initiation complex and their role in presenting tRNA to the complex to initiate translation.

    • Christopher P. Lapointe
    • , Rosslyn Grosely
    •  & Joseph D. Puglisi
  • 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 localization algorithm is applied to datasets obtained with conventional and high-speed atomic force microscopy to increase image resolution beyond the limits set by the radius of the tip used.

    • George R. Heath
    • , Ekaterina Kots
    •  & Simon Scheuring
  • Article |

    Multiplexed imaging of 3,660 chromosomal loci in individual mouse embryonic stem cells by DNA seqFISH+ with immunofluorescence of 17 chromatin marks and subnuclear structures reveals invariant organization of loci within individual cells, and heterogeneous and long-lived distinct combinatorial chromatin states in cellular subpopulations.

    • Yodai Takei
    • , Jina Yun
    •  & Long Cai
  • 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 |

    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 |

    A combination of optical tweezers and fluorescent-particle tracking is used to dissect the dynamics of the Hsp100 disaggregase ClpB, and show that the processive extrusion of polypeptide loops is the mechanistic basis of its activity.

    • Mario J. Avellaneda
    • , Kamila B. Franke
    •  & Sander J. Tans
  • Article |

    Imaging of substrate transport by individual MhsT transporters, members of the neurotransmitter:sodium symporter family of secondary transporters, at single- and multi-turnover resolution reveals that the rate-limiting step varies with the identity of the transported substrate.

    • Gabriel A. Fitzgerald
    • , Daniel S. Terry
    •  & Scott C. Blanchard
  • 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
  • Article |

    A high-affinity complex of histone H1 and prothymosin-α reveals an unexpected interaction mechanism, where the large opposite net charge enables the two proteins to remain highly disordered even in the complex.

    • Alessandro Borgia
    • , Madeleine B. Borgia
    •  & Benjamin Schuler
  • Letter |

    The structure of huntingtin in complex with an interactor is determined to an overall resolution of 4 Å, paving the way for improved understanding of the cellular functions of this protein.

    • Qiang Guo
    • , Bin Huang
    •  & Stefan Kochanek
  • Article |

    Cryo-electron microscopy and single-molecule studies reveal that the adaptors BICDR1 and HOOK3 recruit two dynein molecules to dynactin and thereby increase the force and speed of the dynein–dynactin microtubule motor.

    • Linas Urnavicius
    • , Clinton K. Lau
    •  & Andrew P. Carter
  • Article |

    Single-molecule fluorescence resonance energy transfer is used to identify the rate-limiting step and new intermediates in the conformational cycle of the Listeria monocytogenes calcium transporter LMCA1.

    • Mateusz Dyla
    • , Daniel S. Terry
    •  & Scott C. Blanchard
  • Article |

    The tumour suppressor complex BRCA1–BARD1, which facilitates the generation of a single-stranded DNA template during homologous recombination, also binds to the recombinase RAD51 and enhances its function.

    • Weixing Zhao
    • , Justin B. Steinfeld
    •  & Patrick Sung
  • 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 |

    Hsp70 binds unfolded protein segments in its groove, but can also bind and stabilize folded protein structures, owing to its moveable lid, with ATP hydrolysis and co-chaperones allowing control of these contrasting effects.

    • Alireza Mashaghi
    • , Sergey Bezrukavnikov
    •  & Sander J. Tans
  • Letter |

    Using super-resolution imaging to directly observe the three-dimensional organization of Drosophila chromatin at a scale spanning sizes from individual genes to entire gene regulatory domains, the authors find that transcriptionally active, inactive and Polycomb-repressed chromatin states each have a distinct spatial organisation.

    • Alistair N. Boettiger
    • , Bogdan Bintu
    •  & Xiaowei Zhuang
  • Letter |

    A single-molecule optical tweezer assay is developed to monitor transcription initiation in eukaryotic RNA polymerase II in real-time, making use of a highly purified preinitiation complex (PIC) from yeast; observations show that a large bubble is opened up in the DNA template during initiation, driven by the TFIIH helicase that forms part of the PIC, along with synthesis of an extended transcript before the transition from transcription initiation into elongation.

    • Furqan M. Fazal
    • , Cong A. Meng
    •  & Steven M. Block
  • Letter |

    The Tus–Ter termination site of Escherichia coli is not completely efficient in stopping DNA replication, with about half of replisomes bypassing this blockade; here the speed of the replication machinery is shown to determine the outcome of the encounter between the replisome and Tus–Ter.

    • Mohamed M. Elshenawy
    • , Slobodan Jergic
    •  & Samir M. Hamdan
  • Letter |

    smFRET is used to probe the activation mechanism of two full-length mammalian glutamate receptors, revealing that the extracellular ligand-binding domains of these G-protein-coupled receptors interconvert between three confirmations (resting, activated and a short-lived intermediate state), and that the efficacy of an orthosteric agonist correlates with the degree of occupancy of the active state.

    • Reza Vafabakhsh
    • , Joshua Levitz
    •  & Ehud Y. Isacoff
  • Letter |

    The assembly of single Drosophila RNA-induced silencing complexes (RISCs) is reconstituted using seven purified proteins, revealing that chaperones help stabilize the interaction of the protein heterodimer Dicer-2–R2D2 bound to the short interfering RNA with Ago2.

    • Shintaro Iwasaki
    • , Hiroshi M. Sasaki
    •  & Yukihide Tomari
  • Article |

    An analysis of a bacterial homologue of the human glutamate transporter using single-molecule FRET and X-ray crystallography reveals that opening of the interface between its distinct transport and scaffold domains is rate determining for the transport cycle.

    • Nurunisa Akyuz
    • , Elka R. Georgieva
    •  & Scott C. Blanchard