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| Open AccessAngle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography
Here, using cryo-ET, the 3D structures of individual nucleosome particles were characterized to observe changes under varying ionic strengths and in the presence of protein H1, revealing key regulatory roles in chromatin organization dynamics.
- Meng Zhang
- , César Díaz-Celis
- & Gang Ren
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Article
| Open AccessThe patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane
The Omp85 superfamily is a widely distributed class of outer membrane proteins found in Gram-negative bacteria, mitochondria and chloroplasts. Here the authors show that PlpD has a different structure and topology than other Omp85 proteins that have been studied.
- Sarah E. Hanson
- , Tyrone Dowdy
- & Harris D. Bernstein
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Perspective
| Open AccessRediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery
Temporal blockade of the mononuclear phagocyte system is an approach to enhance the therapeutic efficiency of nanocarrier drug-delivery systems but the broad applicability is hindered by the complexity of optimisation and management of potential side effects. Here, the authors review the development of this technique and show its efficiency using meta-analysis of the published data and discuss essential features for its successful translation to clinic.
- Ivan V. Zelepukin
- , Konstantin G. Shevchenko
- & Sergey M. Deyev
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Article
| Open AccessActive transcription and epigenetic reactions synergistically regulate meso-scale genomic organization
Chromatin within interphase nuclei forms compacted nanoscale DNA domains of uniform size. By integrating theory and imaging, here the authors show how the interplay between transcription and epigenetic mechanisms determine this size, independent of cell type.
- Aayush Kant
- , Zixian Guo
- & Vivek B. Shenoy
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Article
| Open AccessHeliorhodopsin-mediated light-modulation of ABC transporter
Here, authors classify genes flanking the Heliorhodopsin (HeR)-encoding genes and identify highly conserved residues for protein–protein interactions, revealing a function of HeR as regulatory rhodopsin for multidrug resistance.
- Shin-Gyu Cho
- , Ji-Hyun Kim
- & Kwang-Hwan Jung
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Article
| Open AccessThe actin cytoskeleton plays multiple roles in structural colour formation in butterfly wing scales
NCOMMS-23-44446C Vivid structural colours in butterflies are caused by photonic nanostructures scattering light, however insight into the development of such structures in vivo remains scarce. Here the authors show that actin plays a vital and direct templating role during structural colour formation in butterfly scales, providing ridge patterning mechanisms that are likely universal across lepidoptera.
- Victoria J. Lloyd
- , Stephanie L. Burg
- & Andrew J. Parnell
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Article
| Open AccessHigh-throughput mechanical phenotyping and transcriptomics of single cells
The molecular system regulating cell surface mechanics remains largely unexplored at single-cell resolution. Here, the authors report a high-throughput single-cell assay, ELASTomics, which integrates mechanical phenotyping with unbiased transcriptomics.
- Akifumi Shiomi
- , Taikopaul Kaneko
- & Hirofumi Shintaku
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Article
| Open AccessDifferential SNARE chaperoning by Munc13-1 and Munc18-1 dictates fusion pore fate at the release site
How heterogeneously distributed SNARE complexes synchronize fusion pore assemblies during vesicular secretion is unknown. Here, the authors demonstrate a role for SNARE chaperones in coordinating differential release of chemical messengers.
- Bhavya R. Bhaskar
- , Laxmi Yadav
- & Debasis Das
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Article
| Open AccessCorrelative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment
This study combines lattice light sheet microscopy and single molecule imaging to study protein dynamics and chromatin structure in live cells. The authors describe how nucleosomes and proteins move and are organised in relation to chromatin density.
- Timothy A. Daugird
- , Yu Shi
- & Wesley R. Legant
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Article
| Open AccessInterplay between Mg2+ and Ca2+ at multiple sites of the ryanodine receptor
Skeletal ryanodine receptor controls calcium mobilization indispensable for muscle contraction. Here, authors combine cryo-EM and molecular dynamics to uncover the structural basis of the intricate regulation of this channel by calcium and magnesium.
- Ashok R. Nayak
- , Warin Rangubpit
- & Montserrat Samsó
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Article
| Open AccessTRIM25 predominately associates with anti-viral stress granules
Different environmental stressors induce different subtypes of stress granules (SGs), and each of them presumably have distinct functions. Here the authors provide a framework for understanding the compositional and functional heterogeneity of SGs, and see that TRIM25 mainly associates with anti-viral SGs.
- Zehua Shang
- , Sitao Zhang
- & Da Jia
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Article
| Open AccessDynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters
Dynamins are required at nascent endosomes to promote membrane fission. Here, the authors use super-resolution microscopy to show that dynamin-1 recruitment relies on pre-existing nanoclusters and trapping of molecules laterally diffusing on the plasma membrane.
- Anmin Jiang
- , Kye Kudo
- & Frédéric A. Meunier
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Article
| Open AccessMultiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells
In this work, the authors apply polymer models to reconstruct the 3D structure of the genome during SARS-CoV-2 infection and examine how the virus impacts key mechanisms of chromatin organization.
- Andrea M. Chiariello
- , Alex Abraham
- & Mario Nicodemi
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Article
| Open AccessStructural basis of human NOX5 activation
NADPH oxidase 5 (NOX5) is activated by Ca2+ signaling, catalyzing superoxide production by transferring electrons from intracellular NADPH to extracellular oxygen. Here the authors uncover the molecular basis of NOX5 activation and electron transfer.
- Chenxi Cui
- , Meiqin Jiang
- & Ji Sun
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Article
| Open AccessStructural insights into drug transport by an aquaglyceroporin
Pentamidine and melarsoprol are drugs used to treat sleeping sickness caused by Trypanosoma brucei. Here, authors present cryo-EM structures of TbAQP2 with molecular dynamic simulations, revealing mechanisms shaping substrate specificity and drug permeation.
- Wanbiao Chen
- , Rongfeng Zou
- & Chongyuan Wang
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Article
| Open AccessHigh-confidence 3D template matching for cryo-electron tomography
Enabling visual proteomics with high-confidence 3D template matching (TM) in CryoET. 3D TM precisely localizes macromolecular complexes, individual subunits, and different functional states in situ, revealing molecular interactions within cells.
- Sergio Cruz-León
- , Tomáš Majtner
- & Gerhard Hummer
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Article
| Open AccessA nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Here the authors unveil an intermediate state during the folding of the manganese riboswitch from L. lactis. This transient state allows the integration of multiple cellular signals including RNA polymerase pausing and transcription factor NusA.
- Adrien Chauvier
- , Shiba S. Dandpat
- & Nils G. Walter
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Article
| Open Access5′UTR G-quadruplex structure enhances translation in size dependent manner
In eukaryotes, G-quadruplex in mRNA (RG4) 5′ UTR inhibit translation initiation. Here the authors employ single molecule assay to show that RG4 in E. coli reporter increases translation efficiency by preventing ribosome dislodging.
- Chun-Ying Lee
- , Meera Joshi
- & Sua Myong
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Article
| Open AccessPhase-separated droplets swim to their dissolution
Here the authors identify a generic coupling in phase-separated liquids between motility and phase equilibria perturbations: phase-separated droplets swim to their dissolution. This suggests alternative transport mechanism for biomolecular condensates.
- Etienne Jambon-Puillet
- , Andrea Testa
- & Eric R. Dufresne
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Article
| Open AccessStructural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB
KtrAB complex is essential in K+ uptake for bacteria. Here authors illustrate the synergism of ATP and Na+ in activating K+ uptake of KtrAB from Bacillus subtilis and its gating mechanism, which may also shed light on other Na+-activated K+ channels.
- Wesley Tien Chiang
- , Yao-Kai Chang
- & Nien-Jen Hu
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Article
| Open AccessMechanistic basis of the dynamic response of TWIK1 ionic selectivity to pH
Using computer simulations authors identify the dynamic molecular motions controlling the structural conformation of the TWIK1 ion channel, showing that its ability to transport sodium upon acidification result from the evolution of the classical potassium-selective pore.
- Franck C. Chatelain
- , Nicolas Gilbert
- & Olivier Bignucolo
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Article
| Open AccessPharmacological inhibition of α-synuclein aggregation within liquid condensates
Aggregated forms of α-synuclein are characteristic of Parkinson’s disease. Here the authors show that the condensation-driven aggregation pathway of α-synuclein can be inhibited using small molecules: the aminosterol claramine stabilizes α-synuclein condensates and inhibits α-synuclein primary nucleation in the aggregation process.
- Samuel T. Dada
- , Zenon Toprakcioglu
- & Michele Vendruscolo
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Article
| Open AccessSARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds
The main protease, a key enzyme of SARS-CoV-2, can protect itself from oxidative damage. Here, Reinke, Schubert, and colleagues used XFEL radiation to image the enzyme, revealing the disulfide and NOS/SONOS bonds that form in response to oxygen.
- Patrick Y. A. Reinke
- , Robin Schubert
- & Thomas J. Lane
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Article
| Open AccessCardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1
The sodium-calcium exchanger (NCX1) is the primary calcium extrusion mechanism of cardiac myocytes. Here, the authors show that removal of a long questioned allosteric regulation of NCX1 by intracellular sodium alters cardiac excitation-contraction coupling.
- Kyle Scranton
- , Scott John
- & Michela Ottolia
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Article
| Open AccessDeciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis
Here the authors structurally and mechanistically characterize the assembly of FADD, procaspase-8, and cFLIP through their death-effector domains (DEDs), providing insights into the regulation of apoptotic and necroptotic signalling.
- Chao-Yu Yang
- , Chia-I Lien
- & Su-Chang Lin
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Article
| Open AccessGiant organelle vesicles to uncover intracellular membrane mechanics and plasticity
The biophysical properties of cellular organelles are difficult to study directly. Here, the authors generate and characterize osmotically-expanded giant vesicles of several organelles, which maintain some of their functional properties.
- Alexandre Santinho
- , Maxime Carpentier
- & Abdou Rachid Thiam
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Article
| Open AccessAnomalous dynamics of a passive droplet in active turbulence
The fluctuating dynamics of a passive object suspended in an active fluid can provide fundamental insight into the fundamental non-equilibrium behavior of the fluid. Singh and Chaudhuri theoretically investigate the dynamics of a passive deformable droplet in active nematic turbulence and show how the motion of the droplet is influenced by the interplay of spatial correlations of the flow and the size of the droplet.
- Chamkor Singh
- & Abhishek Chaudhuri
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Article
| Open AccessStructural mechanism of voltage-gated sodium channel slow inactivation
Inactivation is an intrinsic property of NaV channel, but the mechanism for slow inactivation is not fully understood. Here, authors show a NaVEh structure in a potential slow-inactivated state, elucidating structural basis for slow inactivation.
- Huiwen Chen
- , Zhanyi Xia
- & Daohua Jiang
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Matters Arising
| Open AccessOn the statistical foundation of a recent single molecule FRET benchmark
- Ayush Saurabh
- , Lance W. Q. Xu
- & Steve Pressé
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Matters Arising
| Open AccessReply to: On the statistical foundation of a recent single molecule FRET benchmark
- Markus Götz
- , Anders Barth
- & Sonja Schmid
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Article
| Open AccessStress-shape misalignment in confluent cell layers
When studying nematic ordering of cells in a monolayer, it is commonly assumed that the principal stress and cell shape axes are tightly coupled. Here, the authors measure cell shape and cell-generated contractile stresses and show that cells in monolayers form correlated, dynamic domains in which the stresses are systematically misaligned with the cell bodies.
- Mehrana R. Nejad
- , Liam J. Ruske
- & Julia M. Yeomans
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Article
| Open AccessProbing the surface charge of condensates using microelectrophoresis
The surface charge and ζ-potential of biomolecular condensates is key to their interactions with membranes and proteins. Here, the authors developed a method to determine the ζ-potential of condensates using microelectrophoresis and single-droplet tracking.
- Merlijn H. I. van Haren
- , Brent S. Visser
- & Evan Spruijt
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Article
| Open AccessDisordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator
Many clock proteins contain intrinsically disordered regions, but how these regions mediate protein interactions is poorly understood. Here, the authors identify charge blocks within a disordered clock protein that regulate circadian timing.
- Meaghan S. Jankowski
- , Daniel Griffith
- & Jennifer M. Hurley
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Article
| Open AccessNMR characterization of RNA binding property of the DEAD-box RNA helicase DDX3X and its implications for helicase activity
DDX3X is a member of the RNA helicase family, which remodels RNA structures. Using solution NMR, here the authors show that DDX3X preferentially binds to single-stranded RNA, which underlies its unwinding activity toward various structured RNA substrates.
- Yuki Toyama
- & Ichio Shimada
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Article
| Open AccessDenaturing mass photometry for rapid optimization of chemical protein-protein cross-linking reactions
Choosing best chemical cross-linking (XL) reagents and conditions for studying protein-protein interactions in structural biology is laborious and lacks in accuracy. The authors develop here an accurate, fast, robust and quantiative denaturing mass photometry approach for screening of XL conditions.
- Hugo Gizardin-Fredon
- , Paulo E. Santo
- & Sarah Cianférani
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Article
| Open AccessThe antimicrobial fibupeptide lugdunin forms water-filled channel structures in lipid membranes
The fibupeptide lugdunin has shown activity against antibiotic-resistant bacteria. Here, authors disclose its mechanism of action in lipid membranes and demonstrate that it assembles into nanotubes facilitating the translocation of monovalent cations.
- Dominik Ruppelt
- , Marius F. W. Trollmann
- & Claudia Steinem
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Article
| Open AccessIFT cargo and motors associate sequentially with IFT trains to enter cilia of C. elegans
Intraflagellar transport is essential for the formation and function of cilia. Here, the authors use single-molecule imaging in live C. elegans to show that transport trains are formed by the sequential attachment of proteins before departing into the cilium.
- Aniruddha Mitra
- , Elizaveta Loseva
- & Erwin J. G. Peterman
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Article
| Open AccessF-actin architecture determines the conversion of chemical energy into mechanical work
F-actin architecture modulates transmission and generation of stresses in cells, yet its impact on myosin ATP hydrolysis remains unknown. The authors perform experiments measuring myosin ATP hydrolysis rates, showing that F-actin architecture can control myosin energy consumption.
- Ryota Sakamoto
- & Michael P. Murrell
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Article
| Open AccessIn situ captured antibacterial action of membrane-incising peptide lamellae
Inspired by the alternating chirality backbone pattern of some effective peptide antimicrobials, here authors design lysine-rich heterochiral peptides that show antimicrobial activity.
- Kamal el Battioui
- , Sohini Chakraborty
- & Tamás Beke-Somfai
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Article
| Open AccessBiomolecular condensates form spatially inhomogeneous network fluids
Here, the authors use small angle neutron scattering and coarse-grained molecular dynamics simulations to demonstrate that condensates based on the granular components of nucleoli are network fluids.
- Furqan Dar
- , Samuel R. Cohen
- & Rohit V. Pappu
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Article
| Open AccessGENESIS CGDYN: large-scale coarse-grained MD simulation with dynamic load balancing for heterogeneous biomolecular systems
Here, the authors report the development of heterogeneous domain decomposition with load balancing for large biological molecular dynamics simulations using residue-level coarse-grained models.
- Jaewoon Jung
- , Cheng Tan
- & Yuji Sugita
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Article
| Open AccessMembrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells
The mechanical properties of heterogeneous cell populations in colorectal tumors and the relevance to cancer metastasis remain not fully understood. Here, the authors suggest that the variations in malignant phenotypes between LGR5-positive cancer stem cells and LGR5-negative cells could be due to their distinct mechanical phenotypes observed in vitro, determined by the membrane to cortex attachment proteins Ezrin/Radixin/Moesin.
- Sefora Conti
- , Valeria Venturini
- & Xavier Trepat
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Article
| Open AccessLocal environment in biomolecular condensates modulates enzymatic activity across length scales
Here, the authors show that biomolecular condensates can enhance enzymatic rates by creating distinct solvent environments compared to the surrounding solution, and this emergent property can manifest within assemblies as small as nanometers.
- Marcos Gil-Garcia
- , Ana I. Benítez-Mateos
- & Paolo Arosio
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Article
| Open AccessRapid evolutionary change in trait correlations of single proteins
Trait correlations impact evolvability as selection on one trait can influence others. Here, the authors examine trait correlation in two proteins, a fluorescent protein & an antibiotic resistance enzyme, observing rapid evolution of trait correlations through changes in the biophysical properties of these proteins.
- Pouria Dasmeh
- , Jia Zheng
- & Andreas Wagner
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Article
| Open AccessMmcA is an electron conduit that facilitates both intracellular and extracellular electron transport in Methanosarcina acetivorans
Methanogens conserve energy through methane generation, however the biochemical details of anaerobic respiration in methanogens remain unclear. Here, authors show a multiheme c-type cytochrome, MmcA, plays a critical role in methanogenesis and anaerobic respiration.
- Dinesh Gupta
- , Keying Chen
- & Dipti D. Nayak
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Article
| Open AccessCryo-EM structures of adenosine receptor A3AR bound to selective agonists
Adenosine A3 receptor (A3AR) holds promise for treating inflammatory and cancer conditions. Here, Cai et al. present cryo-EM structures of A3AR bound to agonists CF101 and CF102, offering insights into its activation and ligand interaction, crucial for developing targeted therapies.
- Hongmin Cai
- , Shimeng Guo
- & H. Eric Xu
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Article
| Open AccessTertiary structure and conformational dynamics of the anti-amyloidogenic chaperone DNAJB6b at atomistic resolution
Adupa et al show how the anti-amyloidogenic molecular chaperone DNAJB6 adopts three conformational states that determine the accessibility of its substrate binding domain. In all states, interactions with HSP70 are shielded, suggesting that functional interactions only may occur upon substrate binding.
- Vasista Adupa
- , Elizaveta Ustyantseva
- & Patrick R. Onck
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Article
| Open AccessFunctional protein dynamics in a crystal
Work by Klyshko and Kim et al. lays the foundation for simulating pump-probe experiments and demonstrates how the dynamic behaviour of proteins extends to the crystal environment, emphasizing the need for an ensemble view in understanding functional motions.
- Eugene Klyshko
- , Justin Sung-Ho Kim
- & Sarah Rauscher
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Article
| Open AccessKdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally
KdpD is known as the sensory histidine kinase of two-component system KdpDE that controls the transcription of the kdpFABC genes. Here, the authors show that KdpD acts as atypical serine kinase, which post-translationally regulates KdpFABC.
- Jakob M. Silberberg
- , Sophie Ketter
- & Inga Hänelt