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| Open AccessSensing the allosteric force
Almost all allosteric systems are large multi-domain proteins which complicates the investigation of the mechanism in atomistic detail. Here authors designed a small allosteric protein system using the photocontrollable PDZ3 domain, that allows controlling allostery between the binding and allosteric site in both directions.
- Olga Bozovic
- , Brankica Jankovic
- & Peter Hamm
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Article
| Open AccessAll atom insights into the impact of crowded environments on protein stability by NMR spectroscopy
The precise effects of crowding on protein folding have been difficult to establish. Here the authors apply multidimensional high-resolution NMR spectroscopy to provide insight on the local impact of macromolecular crowding on the thermodynamic stability of proteins.
- Birgit Köhn
- & Michael Kovermann
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Article
| Open AccessClient proximity enhancement inside cellular membrane-less compartments governed by client-compartment interactions
Membrane-less organelles or compartments are considered to be dynamic reaction centers for spatiotemporal control of diverse cellular processes. Here authors report quantitative measurements of changes in protein interactions for the proteins recruited into membrane-less compartments (termed client proteins) in living cells.
- Daesun Song
- , Yongsang Jo
- & Yongwon Jung
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Article
| Open AccessStructural insights into the mechanism of rhodopsin phosphodiesterase
Rhodopsin phosphodiesterase (Rh-PDE) hydrolyzes both cAMP and cGMP in a light-dependent manner. Structural and functional analyses of the Rh-PDE from Salpingoeca rosetta reveal unusual rhodopsin topology comprising 8 transmembrane helices (TMs) and suggest that TM0 plays a crucial role in the enzymatic photoactivity.
- Tatsuya Ikuta
- , Wataru Shihoya
- & Osamu Nureki
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Article
| Open AccessBehavior control of membrane-less protein liquid condensates with metal ion-induced phase separation
Mimetic membrane-less organelles are of interest for the range of biochemical processes which can be spatio-temporally organized using them. Here, the authors report on a protein condensate system formed by metal ion induced clustering and demonstrate control over condensate properties.
- Kibeom Hong
- , Daesun Song
- & Yongwon Jung
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Article
| Open AccessMolecular mechanisms underlying the extreme mechanical anisotropy of the flaviviral exoribonuclease-resistant RNAs (xrRNAs)
The xrRNA1 RNA from ZIKA virus (ZIKV) forms a complex ring-like architecture and is known for its mechanical anisotropy, but the mechanism for its direction-dependent mechanical responses remain unclear. Here authors use a single-molecule nanopore sensing technique combined with molecular dynamics simulations and show that the anisotropy in ZIKV xrRNA1 depends on Mg2+ and the key tertiary interactions.
- Xiaolin Niu
- , Qiuhan Liu
- & Xianyang Fang
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Article
| Open AccessSensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids
Here, the authors present an approach that enhances the sensitivity of basic 2D biomolecular NMR experiments like NOESY and TOCSY, when carried out in polysaccharides, proteins and nucleic acids. This method combines principles associated to quantum Anti-Zeno Effects and advanced data acquisition methods based on Hadamard multiplexing.
- Mihajlo Novakovic
- , Ēriks Kupče
- & Lucio Frydman
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Article
| Open AccessCombinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions
Multivalent ligand-receptor interactions enhance binding selectivity in biological systems, and may be exploited to design synthetic systems. Here the authors demonstrate a multivalent behavior where the ability to bind the target occurs when the receptor density is within a specific range.
- Meng Liu
- , Azzurra Apriceno
- & Stefano Angioletti-Uberti
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Article
| Open AccessTunable multiphase dynamics of arginine and lysine liquid condensates
The design principles underlying biomolecular phase separation of membrane-less organelles remain poorly understood. Using model homopolymers, Fisher et al. show that the formation kinetics of coexisting liquid phases can be tuned by exploiting differences between arginine and lysine residues.
- Rachel S. Fisher
- & Shana Elbaum-Garfinkle
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Article
| Open AccessMolecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor
SARS-CoV-2 spike protein binds host ACE2 for virus entry. Here, the authors determine kinetic and thermodynamic properties of this interaction using atomic force microscopy, develop peptides that inhibit binding and suggest existence of additional attachment factors.
- Jinsung Yang
- , Simon J. L. Petitjean
- & David Alsteens
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Article
| Open AccessFemtosecond X-ray emission study of the spin cross-over dynamics in haem proteins
The change from low-spin hexacoordinated to high-spin pentacoordinated domed form in heam upon ligand detachment and the reverse process underlie the respiratory function. The authors, using femtosecond time-resolved X-ray emission spectroscopy, capture the transient states connecting the two forms in myoglobin-NO upon NO photoinduced detachment.
- Dominik Kinschel
- , Camila Bacellar
- & Majed Chergui
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Article
| Open AccessR-loop induced G-quadruplex in non-template promotes transcription by successive R-loop formation
G-quadruplex (G4) forming sequences are highly enriched in the human genome and function as important regulators of diverse range of biological processes. Here the authors show that while G4 structures on template strand block transcription, folding on the non-template strand enhances transcription by means of successive R-loop formation.
- Chun-Ying Lee
- , Christina McNerney
- & Sua Myong
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Article
| Open AccessSingle molecule secondary structure determination of proteins through infrared absorption nanospectroscopy
While infrared nanospectroscopy methods based on thermomechanical detection (AFM-IR) enables the acquisition of absorption spectra at the nanoscale, single molecule detection has not been possible so far. Here, the authors present off-resonance, low power and short pulse infrared nanospectroscopy (ORS-nanoIR), which allows measuring infrared absorption spectra at the single molecule level in a time scale of seconds with high throughput and demonstrate that the secondary structure of single protein molecules can be determined with this method.
- Francesco Simone Ruggeri
- , Benedetta Mannini
- & Tuomas P. J. Knowles
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Article
| Open AccessAnisotropic ESCRT-III architecture governs helical membrane tube formation
ESCRT-III proteins assemble into ubiquitous membrane-remodeling polymers during many cellular processes. Here, the authors use cryo-ET, cryo-EM and mathematical modeling to reveal how the shape of the helical membrane tube arises from the assembly of two distinct bundles of helical filaments.
- Joachim Moser von Filseck
- , Luca Barberi
- & Aurélien Roux
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Article
| Open AccessCHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation
Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. Here, the authors use single-molecule assays to examine the mechanism of action of CHD4 remodeller, and provide evidence that CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation.
- Yichen Zhong
- , Bishnu P. Paudel
- & Joel P. Mackay
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Article
| Open AccessLipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness
Proper membrane physiology requires maintenance of a narrow range of physicochemical properties, which must be buffered from external perturbations. Here, authors report lipidomic remodeling to preserve membrane physical properties upon exogenous polyunsaturated fatty acids exposure.
- Kandice R. Levental
- , Eric Malmberg
- & Ilya Levental
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Article
| Open AccessRelaxed sequence constraints favor mutational freedom in idiosyncratic metazoan mitochondrial tRNAs
Bilaterian mitochondria-encoded tRNA genes accumulate mutations at higher rates than their cytoplasmic tRNA counterparts, resulting in idiosyncratic structures. Here the authors suggest an evolutionary basis for the observed mutational freedom of mitochondrial (mt) tRNAs and reveal the associated co-adaptive structural and functional changes in mt aminoacyl-tRNA synthetases.
- Bernhard Kuhle
- , Joseph Chihade
- & Paul Schimmel
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Article
| Open AccessControlled division of cell-sized vesicles by low densities of membrane-bound proteins
Membrane fission of a cell into two daughters is a core ability of cell-based life. Here the authors show that in artificial cells division can be controlled by regulating membrane curvature using low protein density.
- Jan Steinkühler
- , Roland L. Knorr
- & Reinhard Lipowsky
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| Open AccessEukaryotic transcription factors can track and control their target genes using DNA antennas
To carry out their function, transcription factors must efficiently recognize specific DNA sequence targets, a complex problem in the context of eukaryotic chromatin. Here the authors use single-molecule biophysical experiments, statistical mechanical theory and bioinformatics analyses to conclude that interactions with non-target sequences near promoters serve to increase overall affinity and targeting efficiency.
- Milagros Castellanos
- , Nivin Mothi
- & Victor Muñoz
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Article
| Open AccessZinc-finger protein CNBP alters the 3-D structure of lncRNA Braveheart in solution
Many RNA systems possess highly ordered 3-D structures that are essential to their function. Here the authors demonstrate that the long non-coding RNA Braveheart possesses a flexible but defined 3-D structure which is remodeled upon binding the protein CNBP.
- Doo Nam Kim
- , Bernhard C. Thiel
- & Karissa Y. Sanbonmatsu
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Article
| Open AccessMetal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts
Mobile group II introns function as ribozymes to splice and reinsert themselves into DNA, thereby colonizing new genomic regions. Here the authors use single-molecule FRET and molecular dynamics simulations to reveal a structural link between metal ion induced kinetic heterogeneity and the sugar puckers at the exon-intron binding interface.
- Fabio D. Steffen
- , Mokrane Khier
- & Roland K. O. Sigel
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Article
| Open AccessDefinition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ
The repressive states of peroxisome proliferator-activated receptor γ (PPARγ) are ill-defined, despite nuclear receptors being a major drug target. Here authors demonstrate multiple structurally distinct repressive states, providing a structural rationale for ligand bias in a nuclear receptor.
- Zahra Heidari
- , Ian M. Chrisman
- & Travis S. Hughes
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Article
| Open AccessHydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides
Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins plays an important part in the formation of extracellular biological materials. Here, the authors show that repeats of the peptide motif GHGLY are necessary for the LLPS of pH-responsive histidine-rich squid beak proteins.
- Bartosz Gabryelczyk
- , Hao Cai
- & Ali Miserez
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Article
| Open AccessSynthetic protein-conductive membrane nanopores built with DNA
Nanopores have a wide range of applications in the field of sensing. Here the authors report on synthetic nanopores made of DNA and designed for the transit of folded proteins across membranes to allow for biosensing.
- Tim Diederichs
- , Genevieve Pugh
- & Stefan Howorka
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Article
| Open AccessConcerted dynamics of metallo-base pairs in an A/B-form helical transition
Metal-mediated base pairs expand the repertoire of nucleic acid structures and dynamics. Here, the authors prepared a metallo-DNA duplex including two C-Hg(II)-T base pairs separated by six normal Watson-Crick base pairs and investigated its solution structure and dynamics using NMR spectroscopy.
- Olivia P. Schmidt
- , Simon Jurt
- & Nathan W. Luedtke
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Article
| Open AccessOptical mapping of biological water in single live cells by stimulated Raman excited fluorescence microscopy
Recent studies have proposed that intracellular water is different from bulk water at the molecular level. Here the authors introduce a Raman microscopy-based method to image the distribution of water states in living cells, and report intracellular water heterogeneity between nucleus and cytoplasm.
- Lixue Shi
- , Fanghao Hu
- & Wei Min
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Article
| Open AccessSpontaneous ssDNA stretching on graphene and hexagonal boron nitride in plane heterostructures
Single stranded DNA analysis is of interest for a range of applications; however, natural folding of DNA can cause problems with this. Here, the authors report on the in silico analysis of graphene and hexagonal-boron-nitride structures for the stretching and unfolding of DNA to allow for analysis.
- Binquan Luan
- & Ruhong Zhou
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Article
| Open AccessPhotoactivation of silicon rhodamines via a light-induced protonation
Activatable fluorophores are of interest for a wide range of applications but the need for caging groups complicates their development and application. Here, the authors report on a photoactivatable silicon rhodamine derivative and its application in live cell imaging and single-particle tracking.
- Michelle S. Frei
- , Philipp Hoess
- & Kai Johnsson
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Article
| Open AccessFusion dynamics of cubosome nanocarriers with model cell membranes
Understanding the fusion of nanocarriers with cell membranes is important to the design of effective drug delivery methods. Here, the authors report on a study into the fusion of cubosomes with model cell membranes underflow conditions and report on the binding kinetics.
- Brendan P. Dyett
- , Haitao Yu
- & Charlotte E. Conn
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Article
| Open AccessArgonaute bypasses cellular obstacles without hindrance during target search
Argonaute protein is loaded with small RNA and scans long stretch of sequences to find complementary target sites. Here, using single-molecule FRET and kinetic modelling, the authors showed that prokaryotic Argonaute protein binds target DNA loosely and slides along the DNA during target search.
- Tao Ju Cui
- , Misha Klein
- & Chirlmin Joo
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Article
| Open AccessChemical compass behaviour at microtesla magnetic fields strengthens the radical pair hypothesis of avian magnetoreception
Many animals use the Earth’s magnetic field for orientation, yet the underlying principles are poorly understood. The authors show that a molecular triad acts as a chemical compass in magnetic fields of similar magnitude to that of the Earth, supporting the hypothesis that photo-initiated quantum processes underlie bird magnetoreception.
- Christian Kerpal
- , Sabine Richert
- & Christiane R. Timmel
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Article
| Open AccessDiversity of oligomerization in Drosophila semaphorins suggests a mechanism of functional fine-tuning
Semaphorin-plexin interactions regulate various developmental processes in Drosophila but the structural basis of these signaling events is unclear. Here, the authors present crystal structures of all Drosophila class 1 and 2 semaphorins, and elucidate determinants for their plexin binding specificities.
- Daniel Rozbesky
- , Ross A. Robinson
- & E. Yvonne Jones
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Article
| Open AccessDesign and fabrication of flexible DNA polymer cocoons to encapsulate live cells
The ability to encapsulate living cells could lead to many applications. Here, the authors present a flexible method to graft DNA polymers onto bacteria, yeast and mammalian cells, polymerize them into DNA cocoons and use these to manipulate and select cells based on the encoded polymer sequences on DNA cocoons.
- Tao Gao
- , Tianshu Chen
- & Genxi Li
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Article
| Open AccessStructural basis for functional interactions in dimers of SLC26 transporters
The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. Here, the authors resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize it by PELDOR/DEER distance measurements, biochemical studies with MD simulations and spin-label ensemble refinement.
- Yung-Ning Chang
- , Eva A. Jaumann
- & Eric R. Geertsma
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Article
| Open AccessSide chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor
Polyglutamine (polyQ) tracts are low-complexity regions and their expansion is linked to certain neurodegenerative diseases. Here the authors combine experimental and computational approaches to find that the length of the androgen receptor polyQ tract correlates with its helicity and show that the polyQ helical structure is stabilized by hydrogen bonds between the Gln side chains and main chain carbonyl groups.
- Albert Escobedo
- , Busra Topal
- & Xavier Salvatella
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Article
| Open AccessConformational dynamics of the human serotonin transporter during substrate and drug binding
The serotonin transporter (SERT) is responsible for re-uptake of serotonin into the presynaptic neuron and plays a key role in synaptic transmission. Here, the authors use hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs.
- Ingvar R. Möller
- , Marika Slivacka
- & Kasper D. Rand
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Article
| Open AccessPhotoregulated fluxional fluorophores for live-cell super-resolution microscopy with no apparent photobleaching
Super-resolution microscopy with spontaneously blinking dyes is dependent on pH and polarity of the medium. Here the authors introduce a photoactivatable fluxional fluorophore for live cell imaging that allows control over the fraction of spontaneously blinking molecules independently of medium properties.
- Elias A. Halabi
- , Dorothea Pinotsi
- & Pablo Rivera-Fuentes
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Article
| Open AccessDynamic pigmentary and structural coloration within cephalopod chromatophore organs
Chromatophores in cephalopod skin are known for fast changes in coloration due to light-scattering pigment granules. Here, authors demonstrate structural coloration facilitated by reflectin in sheath cells and offer insights into the interplay between structural and pigmentary coloration elements.
- Thomas L. Williams
- , Stephen L. Senft
- & Leila F. Deravi
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Article
| Open AccessA five-residue motif for the design of domain swapping in proteins
Designing interfaces that can induce protein-protein interactions is a challenging problem. Here the authors show that a five amino acid sequence known to mediate domain swapping in cystatins can drive oligomerization when grafted onto functionally and structurally unrelated host proteins, providing a simple approach to the design of protein assemblies.
- Neha Nandwani
- , Parag Surana
- & Shachi Gosavi
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Article
| Open AccessAn automated Bayesian pipeline for rapid analysis of single-molecule binding data
Analysis of single-molecule binding assays still requires substantial manual user intervention. Here, the authors present a pipeline for rapid, automated analysis of co-localization single-molecule spectroscopy images, with a modular user interface that can be adjusted to a range of experimental conditions.
- Carlas S. Smith
- , Karina Jouravleva
- & David Grunwald
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Article
| Open AccessObservation of dissociative quasi-free electron attachment to nucleoside via excited anion radical in solution
Radiation-induced low-energy electrons in solution are implicated in DNA damage, but their relaxation dynamics are not well understood. Here the authors observe how quasi-free electrons dissociate glycosidic bonds via an excited nucleoside anion radical, whereas solvated electrons reside on the nucleoside as a relatively stable anion radical.
- Jun Ma
- , Anil Kumar
- & Mehran Mostafavi
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Article
| Open AccessMembrane water for probing neuronal membrane potentials and ionic fluxes at the single cell level
Non-invasive spatiotemporal probing of electric potentials in living neurons without chemical or genetic modification provides a major advancement to neuroscience. Here, the authors demonstrate the use of membrane water as a probe for neuronal membrane potentials and ionic flux.
- M. E. P. Didier
- , O. B. Tarun
- & S. Roke
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Article
| Open AccessNanoribbons self-assembled from short peptides demonstrate the formation of polar zippers between β-sheets
Peptide self-assembly is a hierarchical process which includes forming β-sheets but the formation of high ordered structures remains largely unexplored. Here the authors report on a super-secondary structural template, based on well-defined hydrogen bonds by rational design and assembly of short peptides
- Meng Wang
- , Jiqian Wang
- & Hai Xu
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Article
| Open AccessA proline switch explains kinetic heterogeneity in a coupled folding and binding reaction
How intrinsically disordered proteins (IDPs) undergo a coupled folding and binding reaction with their molecular targets remains to be understood. Here authors use single-molecule FRET to assess the contribution of cis/trans isomerization of peptidyl-prolyl bonds in regulating IDP interactions.
- Franziska Zosel
- , Davide Mercadante
- & Benjamin Schuler
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Article
| Open AccessForcing the reversibility of a mechanochemical reaction
Mechanical force can facilitate thermodynamically unfavourable reactions. Here, the authors found that a stretching force can promote the SN2 cleavage of a protein disulfide bond by weak nucleophilic thiols, and that removing this force reverses the reaction yielding the original disulfide bond.
- Amy E. M. Beedle
- , Marc Mora
- & Sergi Garcia-Manyes
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Article
| Open AccessMolecular insights into antibiotic resistance - how a binding protein traps albicidin
The potent antibacterial compound albicidin is synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. Here the authors employ a multidisciplinary approach and provide structural and mechanistic insights into how the drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca.
- Lida Rostock
- , Ronja Driller
- & Roderich D. Süssmuth
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Article
| Open AccessHow nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins
In Escherichia coli, outer membrane protein (OMP) cluster and form islands, but the origin and behaviour of those clusters remains poorly understood. Here authors use coarse grained molecular dynamics simulation and show that their mesoscale simulations recapitulate the restricted diffusion characteristics of OMPs.
- Matthieu Chavent
- , Anna L. Duncan
- & Mark S. P. Sansom
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Article
| Open AccessDirect observation of DNA target searching and cleavage by CRISPR-Cas12a
Cas12a is a RNA-guided DNA endonuclease whose detailed mechanisms of target searching and DNA cleavage remained unclear. Here authors use single-molecule fluorescence assays to show that Cas12a searches for their on-target site.
- Yongmoon Jeon
- , You Hee Choi
- & Sangsu Bae
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Article
| Open AccessSingle-molecule insights into surface-mediated homochirality in hierarchical peptide assembly
Most chiral molecules and structures in living organisms exist as single enantiomers, but why? Here, the authors investigated surface-mediated homochirality on the single-molecule level and show that it can be triggered by the chirality unbalance of two adsorption configuration monomers.
- Yumin Chen
- , Ke Deng
- & Chen Wang