Single-molecule biophysics articles within Nature Communications

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  • Article
    | Open Access

    Direct visualization of the structural transformation from pre-pore to pore of the mammalian immune defense complex perforin-2 (PFN2) reveals a clockwise hand-over-hand mechanism that propagates at ~15 subunits per second.

    • Fang Jiao
    • , François Dehez
    •  & Simon Scheuring

  • Article
    | Open Access

    Most eukaryotes do not use a consensus DNA sequence as binding sites for the origin recognition complex (ORC) to initiate DNA replication, however budding yeast do. Here the authors show S. cerevisiae ORC can bind nucleosomes near nucleosome-free regions and recruit replicative helicases to form a pre-replication complex independent of the DNA sequence.

    • Sai Li
    • , Michael R. Wasserman
    •  & Shixin Liu

  • Article
    | Open Access

    Dynamic remodeling of the actin cytoskeleton underlies cell movement, but is challenging to characterize at the molecular level. Here, the authors present a method to extract actin filament velocities in living cells, and compare their results to current models of cytoskeletal dynamics.

    • Cayla M. Miller
    • , Elgin Korkmazhan
    •  & Alexander R. Dunn

  • Article
    | Open Access

    Pulsed electron-electron double resonance spectroscopy (PELDOR/DEER) and single-molecule Förster resonance energy transfer spectroscopy (smFRET) are used to determine conformational changes and probe distances in biological macromolecules. Here the authors compare the methods on a large set of samples.

    • Martin F. Peter
    • , Christian Gebhardt
    •  & Gregor Hagelueken

  • Article
    | Open Access

    Here the authors used single-molecule imaging and manipulation to study the mechanical effects of transcription factor Sox2 co-condensation with DNA and chromatin. They found that Sox2 condensates exert a high level of mechanical stress on DNA, but this stress is dramatically attenuated by nucleosomes assembled on the DNA.

    • Tuan Nguyen
    • , Sai Li
    •  & Shixin Liu

  • Article
    | Open Access

    EGFR regulates cellular processes across the animal kingdom. Here, the authors show that transmembrane conformational coupling is the first step in EGFR signaling, providing evidence for the existence of transmembrane intramolecular conformational changes in a single pass membrane protein.

    • Shwetha Srinivasan
    • , Raju Regmi
    •  & Gabriela S. Schlau-Cohen

  • Article
    | Open Access

    Conductive events during nanopore sensing, are seen typically under low salt conditions and widely thought to arise from counterions brought into the pore via analyte. Here, authors show that an imbalance of ionic fluxes lead to conductive events.

    • Lauren S. Lastra
    • , Y. M. Nuwan D. Y. Bandara
    •  & Kevin J. Freedman

  • Article
    | Open Access

    Gasdermin-A3 pore formation propagates along diverse pathways. It begins with membrane attachment and oligomeric pre-assembly. Once inserted in the membrane, the oligomers re-assemble into various shapes and sizes, which open their lytic pores.

    • Stefania A. Mari
    • , Kristyna Pluhackova
    •  & Daniel J. Müller

  • Article
    | Open Access

    The Mre11-Rad50 (MR) complex has key functions in the detection, signaling and repair of DNA breaks. Here the authors use transmission electron microscopy to show MR oligomerization is governed by a small beta-sheet protruding from the head domain of Rad50 at the base of the MR structure, and reveal MR head domain oligomerization is required for efficient DNA end resection.

    • Vera M. Kissling
    • , Giordano Reginato
    •  & Matthias Peter

  • Article
    | Open Access

    Single molecule detection based on evanescent illumination usually require specially designed nanomaterials. Here, the authors show that single molecule detection can be realised on a plain glass surface via interference between the evanescent lights scattered by molecules and the natural roughness of the glass.

    • Pengfei Zhang
    • , Lei Zhou
    •  & Shaopeng Wang

  • Article
    | Open Access

    Metelev et al. use single-molecule tracking to study kinetics of translation directly in E. coli cells, and how it is affected by translation inhibitors and rRNA mutations. Their results support widespread 70S re-initiation on mRNAs.

    • Mikhail Metelev
    • , Erik Lundin
    •  & Magnus Johansson

  • Article
    | Open Access

    The authors introduce optical horn antennas, a nanophotonic platform combining plasmonic enhancement, efficient collection and background screening, for detection of UV autofluorescence from single proteins. They demonstrate label-free monitoring of protein unfolding and dissociation upon denaturation.

    • Aleksandr Barulin
    • , Prithu Roy
    •  & Jérôme Wenger

  • Article
    | Open Access

    RecBCD is a remarkably fast DNA helicase. Using a battery of biophysical methods, Zananiri et. al reveal additional, non-catalytic ATP binding sites that increase the ATP flux to the catalytic sites that allows fast unwinding when ATP is scarce.

    • Rani Zananiri
    • , Sivasubramanyan Mangapuram Venkata
    •  & Arnon Henn

  • Article
    | Open Access

    For decades, miRNAs have been studied primarily by ensemble methods, where a bulk collection of molecules is measured outside cells. Here, Kobayashi and Singer report methods to image miRNA function at the single-molecule level inside cells.

    • Hotaka Kobayashi
    •  & Robert H. Singer

  • Article
    | Open Access

    In this work, the authors demonstrate the application of multi-parameter photon-by-photon hidden Markov modeling (mpH2MM) on alternating laser excitation (ALEX)-based smFRET measurements. The utility of mpH2MM in identifying and quantifying dynamic biomolecular sub-populations is demonstrated in three different systems.

    • Paul David Harris
    • , Alessandra Narducci
    •  & Eitan Lerner

  • Article
    | Open Access

    Nanopores are powerful tools for sampling protein-peptide interactions. Here, the authors convert a protein-based nanopore into a sensitive biosensor to characterize the complex binding of WDR5 protein to a 14-residue ligand.

    • Lauren Ashley Mayse
    • , Ali Imran
    •  & Liviu Movileanu

  • Article
    | Open Access

    Here the authors probe the cleavage and gate opening of single-stranded DNA by the human topoisomerase TRR using a unique single-molecule strategy to reveal structural plasticity in response to both double-stranded DNA and the helicase BLM.

    • Julia A. M. Bakx
    • , Andreas S. Biebricher
    •  & Erwin J. G. Peterman

  • Article
    | Open Access

    GPCR kinases (GRKs) phosphorylate active-form G-protein-coupled receptors (GPCRs). Here, the authors reveal that Gq heterotrimer coupled with the angiotensin II type-1 receptor (AT1R) determines the GRK subtypes recruited to the complex in a microdomain, thus defining subsequent AT1R phosphorylation patterns, β-arrestin conformation and functionality.

    • Kouki Kawakami
    • , Masataka Yanagawa
    •  & Asuka Inoue

  • Article
    | Open Access

    A single molecule fluorescence study revealed three dynamically interconverting conformations of the fluoride riboswitch from Bacillus cereus, where an anionic ligand snap-locks a docked conformation through a long-range interaction necessary for downstream gene regulation.

    • Rajeev Yadav
    • , Julia R. Widom
    •  & Nils G. Walter

  • Article
    | Open Access

    Chiral communication can propagate in secondary structures within the effective intermolecular force (IMF) range but it is not known whether long-range chiral communication exists between tertiary peptide structures. Here, the authors use single-molecule force spectroscopy to investigate chiral interaction between DNA duplexes/triplexes and peptide coiled-coils and demonstrate chiral communication beyond the IMF distance.

    • Shankar Pandey
    • , Shankar Mandal
    •  & Hanbin Mao

  • Article
    | Open Access

    Here, the authors use high-speed atomic force microscopy (HS-AFM) methods to characterize the single molecule kinetics of wild-type bacteriorhodopsin (bR) with millisecond temporal resolution, providing new insights into the bR conformational cycle.

    • Alma P. Perrino
    • , Atsushi Miyagi
    •  & Simon Scheuring

  • Article
    | Open Access

    UvrD is a model helicase from the non-hexameric Superfamily 1. Here, the authors use optical tweezers to measure directly the stepwise translocation of UvrD along a DNA hairpin, and propose a mechanism in which UvrD moves one base pair at a time, but sequesters the nascent single strands, releasing them after a variable number of ATP hydrolysis cycles.

    • Sean P. Carney
    • , Wen Ma
    •  & Yann R. Chemla

  • Article
    | Open Access

    Revealing mechanisms of complex protein machines requires simultaneous exploration of multiple structural coordinates. Here the authors report two-colour fluorescence microscopy combined with photoinduced electron transfer probes to simultaneously detect two structural coordinates in single protein molecules.

    • Jonathan Schubert
    • , Andrea Schulze
    •  & Hannes Neuweiler

  • Article
    | Open Access

    In viruses, multi-subunit ring-ATPases are involved in genome packaging. Here, using single-molecule techniques, the authors determine that the active bacteriophage T4 DNA packaging motor is a pentamer and show that the motor can tolerate inactive subunits, suggesting that strict coordination between the subunits is not crucial.

    • Li Dai
    • , Digvijay Singh
    •  & Venigalla B. Rao

  • Article
    | Open Access

    An enzymatic ensemble including Dna2 functions in DNA end resection; the function of the single-stranded DNA binding protein RPA in this complex has been underappreciated. Here the authors employ molecular modeling, biochemistry, and single molecule biophysics to reveal RPA directly promotes Dna2 recruitment, nuclease and helicase activities.

    • Ananya Acharya
    • , Kristina Kasaciunaite
    •  & Petr Cejka

  • Article
    | Open Access

    Here the authors use nanovesicles, microfluidics and single-molecule methods to observe individual ligand binding events that stimulate activation of CNG ion channels. They find that binding is followed by a conformational change of either independent or weakly cooperative binding domains.

    • Vishal R. Patel
    • , Arturo M. Salinas
    •  & Marcel P. Goldschen-Ohm

  • Article
    | Open Access

    Deviations from Brownian motion leading to anomalous diffusion are ubiquitously found in transport dynamics but often difficult to characterize. Here the authors compare approaches for single trajectory analysis through an open competition, showing that machine learning methods outperform classical approaches.

    • Gorka Muñoz-Gil
    • , Giovanni Volpe
    •  & Carlo Manzo

  • Article
    | Open Access

    Molecular chaperones from the Hsp70 family can break up protein aggregates, including amyloids. Here, the authors utilize microfluidic diffusional sizing to assess the mechanism of α-synuclein (αS) disaggregation by the Hsc70–DnaJB1–Apg2 system, and show that single αS molecules are removed directly from the fibril ends.

    • Matthias M. Schneider
    • , Saurabh Gautam
    •  & Tuomas P. J. Knowles

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