Featured
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Super-resolution labelling with Action-PAINT
Super-resolution microscopy has enabled optical imaging of individual biomolecules on the nanometre scale. Now, a new method has been developed that allows active manipulation of single-molecule targets on visualization in a sequential manner. This method, called ‘Action-PAINT’, combines real-time super-resolution microscopy (DNA-PAINT) and photoinducible crosslinking chemistry to deliver a single-molecule cargo with <30 nm selectivity.
- Ninning Liu
- , Mingjie Dai
- & Peng Yin
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Temperature-jump solution X-ray scattering reveals distinct motions in a dynamic enzyme
Understanding how structural dynamics contribute to protein function is a longstanding challenge in structural biology. Now, time-resolved X-ray solution scattering following an infrared laser-induced temperature jump has been used to probe functional, intramolecular motions in the dynamic enzyme cyclophilin A.
- Michael C. Thompson
- , Benjamin A. Barad
- & James S. Fraser
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Stimulus-responsive self-assembly of protein-based fractals by computational design
Fractal topologies are ubiquitous, and synthetic fractal objects provide unique functional advantages by virtue of their high surface area:volume ratios. Now, a computationally guided bottom-up design approach for constructing protein-based fractal assemblies in response to phosphorylation has been developed. Designed assemblies are shown to perform reversible and efficient molecular capture.
- Nancy E. Hernández
- , William A. Hansen
- & Sagar D. Khare
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Maleimide–thiol adducts stabilized through stretching
Single-molecule force spectroscopy reveals that maleimide–thiol adducts can be stabilized by stretching through a force-dependent kinetic control mechanism. This unconventional use of mechanochemistry enabled us to produce stable polymer–protein conjugates by simply applying a mechanical force to the maleimide–thiol adducts through mild ultrasonication.
- Wenmao Huang
- , Xin Wu
- & Yi Cao
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A fluorescent membrane tension probe
Lipid membranes—which separate cells and organelles from their environment—experience tension during various cell processes; however, measuring membrane tension is notoriously difficult. Now, a new fluorescent, mechanosensitive membrane probe called FliptR has been developed. FliptR enables simple, direct membrane tension measurements in cellular and artificial membranes.
- Adai Colom
- , Emmanuel Derivery
- & Aurélien Roux
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Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels
That K+ channels conduct K+ ions at near-diffusion limited rates, but block the passage of smaller Na+ ions, creates an apparent contradiction. Now, atomistic simulations and free-energy calculations are used to show that both K+ permeation and ion selectivity are governed by the direct knock-on of completely desolvated ions in the channels’ selectivity filter.
- Wojciech Kopec
- , David A. Köpfer
- & Ulrich Zachariae
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Towards simple kinetic models of functional dynamics for a kinase subfamily
Molecular dynamics simulations for seven members of the Src kinase family have now revealed a conserved step-wise deactivation process, potentially druggable intermediate states, and quantitatively similar thermodynamics and kinetics across the entire family.
- Mohammad M. Sultan
- , Gert Kiss
- & Vijay S. Pande
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Infrared spectroscopy reveals multi-step multi-timescale photoactivation in the photoconvertible protein archetype dronpa
Understanding the mechanism of photoconversion in fluorescent proteins is essential to optimizing applications in imaging and optogenetics. It has now been demonstrated that photoconversion in the photoswitchable protein dronpa follows a multi-step mechanism, with both chromophore and protein structural dynamics occurring on multiple timescales from picoseconds to hundreds of microseconds.
- Sergey P. Laptenok
- , Agnieszka A. Gil
- & Stephen R. Meech
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Predicting DNA hybridization kinetics from sequence
The rate constant of DNA hybridization varies over several orders of magnitude and is affected by temperature and DNA sequence. A machine-learning algorithm that is capable of accurately predicting hybridization rate constants has now been developed. Tests with this algorithm showed that over 90% of predictions were correct to within a factor of three.
- Jinny X. Zhang
- , John Z. Fang
- & David Yu Zhang
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Single-molecule spectroscopy of LHCSR1 protein dynamics identifies two distinct states responsible for multi-timescale photosynthetic photoprotection
Photoprotection is crucial for the fitness of organisms that carry out oxygenic photosynthesis. LHCSR, a photosynthetic light-harvesting complex, has been implicated in photoprotection in green algae and moss. Now, single-molecule studies of LHCSR have revealed that multi-timescale protein dynamics underlie photoprotective dissipation of excess energy.
- Toru Kondo
- , Alberta Pinnola
- & Gabriela S. Schlau-Cohen
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Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles
Ultrafast-scanning fluorescence correlation spectroscopy has now been used to measure the molecular interactions underlying the phase behaviour of disordered proteins. Sequence-encoded conformational fluctuations of these proteins are shown to give rise to phase-separated droplets of surprisingly low concentrations. These results provide insight into how the structural features of the droplets affect the properties of liquid-phase intracellular organelles.
- Ming-Tzo Wei
- , Shana Elbaum-Garfinkle
- & Clifford P. Brangwynne
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Placing and shaping liposomes with reconfigurable DNA nanocages
Controlling liposome shape, arrangement and dynamics is important for biophysical studies and synthetic biology applications. Now, using a family of reconfigurable DNA nanocages as templates, spherical, tubular, toroidal and helical liposomes with predefined geometry have been produced. DNA-guided membrane fusion and bending is also demonstrated.
- Zhao Zhang
- , Yang Yang
- & Chenxiang Lin
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Complete protein–protein association kinetics in atomic detail revealed by molecular dynamics simulations and Markov modelling
Uncovering the microscopic details of protein–protein association via direct molecular dynamics (MD) simulations has been prevented by the excessive lifetimes of associated states. Now, association and dissociation for the barnase–barstar complex has been studied by adaptive high-throughput MD simulations and Markov modelling, revealing intermediate structures, energetics and kinetics on microseconds-to-hours timescales.
- Nuria Plattner
- , Stefan Doerr
- & Frank Noé
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Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases
Despite decades of research into heme-copper oxidases, the advantages provided by copper over iron as the non-heme metal has remained unclear. Now, the preference of copper over iron has finally been explained. Copper favours faster electron transfer and higher O–O bond activation, which results in much higher oxidase activity than would be achieved by an iron equivalent.
- Ambika Bhagi-Damodaran
- , Matthew A. Michael
- & Yi Lu
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Cell-sized asymmetric lipid vesicles facilitate the investigation of asymmetric membranes
Cell-sized asymmetric giant lipid vesicles containing a very small amount of organic solvent have now been formed via inhomogeneous break-up of a lipid microtube that was generated by applying a jet flow to an asymmetric planar lipid bilayer. The asymmetric giant vesicles were used to investigate the dynamic responses of lipid molecules and the effect of asymmetry on biochemical reactions.
- Koki Kamiya
- , Ryuji Kawano
- & Shoji Takeuchi
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News & Views |
Proton fronts on membranes
Proton migration on membranes is a crucial step in the bioenergetics of the cell. It has typically been regarded as slow successive proton transfers between ionizable moieties within the membrane, but recent measurements suggest fast lateral diffusion in the membrane's hydration layer.
- Noam Agmon
- & Menachem Gutman
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A sequence-specific threading tetra-intercalator with an extremely slow dissociation rate constant
Molecules that bind to DNA for extended periods can modulate its transcription or other biological processes. Kinetic studies on the non-covalent complex formed by a threading tetra-intercalator and a DNA double-helix have now revealed a multi-step association, and a particularly slow dissociation leading to sequence specificity and a 16-day half-life.
- Garen G. Holman
- , Maha Zewail-Foote
- & Brent L. Iverson
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Mutual modulation between membrane-embedded receptor clustering and ligand binding in lipid membranes
Using a chemical model, the binding of a monovalent ligand and the clustering of a membrane-embedded receptor are shown to be closely related processes that modulate each other without the contribution of any apparent multivalence effect.
- Salvador Tomas
- & Lilia Milanesi
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News & Views |
Interface influence
The aggregation of proteins into fibrils plays a crucial role in neurological conditions such as Parkinson's disease. Further insight into fibril formation has now been gained that reveals the effect of hydrophobic surfaces, including air.
- Ian W. Hamley
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A polyhedron made of tRNAs
Whereas synthetic DNA nanostructures are widely studied, the use of RNA as a structural building block is much less common. Now, it has been shown that tRNA molecules can be designed to assemble into a rigid and thermally stable square antiprism structure that may prove useful for delivery applications inside cells.
- Isil Severcan
- , Cody Geary
- & Luc Jaeger
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News & Views |
Springing into action
Controlling the movements of molecular systems through external stimuli is crucial for the construction of nanoscale mechanical machines. A spring-like compound has now been prepared — a double helicate that retains its handedness under ion-triggered extension and contraction.
- Ben L. Feringa
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Enhancement of anhydrous proton transport by supramolecular nanochannels in comb polymers
Efficient conduction of protons on a micrometre scale is critical for the development of fuel cell membranes — a key component of clean energy sources. Now, self-assembling amphiphilic polymers have been shown to provide a nanoscale organization of proton-conducting functionalities that dramatically increases anhydrous proton conductivity.
- Yangbin Chen
- , Michael Thorn
- & S. Thayumanavan
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Research Highlights |
Sticky situation
The sliding movement of the actin–myosin protein conjugate responsible for contracting muscles can be inhibited using a dendrimer that glues them together.
- Gavin Armstrong