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Single-molecule dynamics show a transient lipopolysaccharide transport bridge
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
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Article |
Cryo-EM structure of the human cardiac myosin filament
The intricate molecular architecture and interactions of the human cardiac myosin filament offer insights into cardiac physiology, disease and drug therapy.
- Debabrata Dutta
- , Vu Nguyen
- & Roger Craig
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Article
| Open AccessStructure and electromechanical coupling of a voltage-gated Na+/H+ exchanger
Upon hyperpolarization, the S4 voltage-sensing segment of sea urchin SLC9C1 moves down, removing inhibition caused by an intracellular helix and enabling Na+/H+ exchange, leading to pH-dependent activation of sAC and sperm chemotaxis.
- Hyunku Yeo
- , Ved Mehta
- & David Drew
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Article
| Open AccessStructures of a sperm-specific solute carrier gated by voltage and cAMP
This study proposes a molecular mechanism of voltage activation in SLC9C1, a transporter essential for male fertility.
- Valeria Kalienkova
- , Martin F. Peter
- & Cristina Paulino
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News & Views |
Protein condensation regulates water availability in cells
Proteins can condense to form membraneless organelles, which act as vessels for biochemical reactions in cells. An investigation shows that protein condensation is also a cellular mechanism for controlling water availability.
- J. Pedro de Souza
- & Howard A. Stone
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Article
| Open AccessMacromolecular condensation buffers intracellular water potential
Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.
- Joseph L. Watson
- , Estere Seinkmane
- & Emmanuel Derivery
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Article |
A bioelectrical phase transition patterns the first vertebrate heartbeats
The first heartbeat of a zebrafish was captured, and development of cardiac excitability and conduction around this singular event were analysed, showing how development of single-cell properties produces a transition from quiescence to coordinated beating.
- Bill Z. Jia
- , Yitong Qi
- & Adam E. Cohen
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Article |
A pentameric TRPV3 channel with a dilated pore
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
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News & Views |
Dynamic ion channel defies dogma
It is well established that proteins in the TRP family of ion channels assemble from four subunits. But do they always do this? A five-subunit structure has now been observed, and might be involved in channel regulation.
- Ute A. Hellmich
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Article
| Open AccessDirect observation of the conformational states of PIEZO1
The plasma membrane can expand the blades of the PIEZO1 ion channel, impacting channel activation.
- Eric M. Mulhall
- , Anant Gharpure
- & Ardem Patapoutian
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Structure of an endogenous mycobacterial MCE lipid transporter
Proteins of the Mycobacterium smegmatis Mce1 system assemble to form an elongated ABC transporter complex that is long enough to span the impermeable mycobacterial cell envelope.
- James Chen
- , Alice Fruhauf
- & Damian C. Ekiert
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News & Views |
Dynamics of protein droplets revealed by bridging multiple scales
Many biological processes rely on proteins that aggregate into droplets governed by dynamics that span myriad scales. A clever combination of spectroscopy and simulation offers a way to probe these diverse dynamics.
- Marina G. Guenza
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Research Briefing |
Protein folding stability measured at scale
Protein sequences vary widely in their folding stabilities (the energetic favourability of folded compared with unfolded conformations), and protein alterations that affect stability have profound effects on evolution, health and disease, and biotechnological applications. An innovative method has made it possible to measure these stabilities on a massive scale, revealing evolutionary trends and opening up possibilities for machine learning.
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Extreme dynamics in a biomolecular condensate
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
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| Open AccessMega-scale experimental analysis of protein folding stability in biology and design
Large-scale assays using cDNA display proteolysis are used to measure the folding stabilities of protein domains, providing a method to quantify the effects of mutations on protein folding, with applications in protein design.
- Kotaro Tsuboyama
- , Justas Dauparas
- & Gabriel J. Rocklin
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Structural insights into BCDX2 complex function in homologous recombination
Analyses of the structure and biochemical properties of the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 reveal details of its role in the repair of DNA double-strand breaks.
- Yashpal Rawal
- , Lijia Jia
- & Shaun K. Olsen
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Article
| Open AccessSingle-photon absorption and emission from a natural photosynthetic complex
Using a heralded single-photon source along with coincidence counting, we establish time correlation functions for B800 excitation and B850 fluorescence emission and demonstrate that both events involve single photons.
- Quanwei Li
- , Kaydren Orcutt
- & K. Birgitta Whaley
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Technology Feature |
Powerful microscope captures motor proteins in unprecedented detail
Called MINFLUX, the super-resolution method allows researchers to track molecules under cellular conditions.
- Amanda Heidt
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Article |
Outer membrane utilisomes mediate glycan uptake in gut Bacteroidetes
A structural and functional analysis of the systems involved in oligosaccharide uptake in gut Bacteroidetes describes multicomponent complexes termed utilisomes that include pre-processing and transport subunits.
- Joshua B. R. White
- , Augustinas Silale
- & Neil A. Ranson
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News |
The human brain’s characteristic wrinkles help to drive how it works
A model of the brain’s geometry better explains neuronal activity than a model based on the ‘connectome’.
- Davide Castelvecchi
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Article
| Open AccessÅngström-resolution fluorescence microscopy
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
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Article
| Open AccessStructural basis of NINJ1-mediated plasma membrane rupture in cell death
Structural, biochemical and mutagenesis studies indicate that, in dying cells, the membrane protein NINJ1 assembles into filaments, disrupting the cell membrane.
- Morris Degen
- , José Carlos Santos
- & Sebastian Hiller
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RNA conformational propensities determine cellular activity
Systematic alteration of HIV-1 TAR RNA and quantitative determination of its propensity to bind to the Tat protein establish a key role role for a rare and short-lived RNA state in Tat-dependent transactivation in cells.
- Megan L. Ken
- , Rohit Roy
- & Hashim M. Al-Hashimi
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EMC chaperone–CaV structure reveals an ion channel assembly intermediate
Interactions between the endoplasmic reticulum membrane protein complex (EMC) and the high-voltage-activated calcium channel CaVα2δ are mutually exclusive, and EMC-to-CaVα2δ hand-off involves a divalent ion-dependent step and CaV1.2 element ordering.
- Zhou Chen
- , Abhisek Mondal
- & Daniel L. Minor Jr
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Peroxisome biogenesis initiated by protein phase separation
A study presents evidence to support a model in which liquid–liquid phase separation of components of the transport machinery mediates formation of transient protein transport channels on peroxisomes.
- Rini Ravindran
- , Isabel O. L. Bacellar
- & Stephen W. Michnick
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De novo evolution of macroscopic multicellularity
After 600 rounds of selection, anaerobic snowflake yeast evolved to be macroscopic, becoming around 20,000 times larger (approximately mm scale) and about 10,000-fold more biophysically tough, while retaining a clonal multicellular life cycle.
- G. Ozan Bozdag
- , Seyed Alireza Zamani-Dahaj
- & William C. Ratcliff
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Article
| Open AccessStructural evidence for intermediates during O2 formation in photosystem II
Using serial femtosecond X-ray cystallography, we provide structural insights into the final reaction step of Kok’s photosynthetic water oxidation cycle, specifically the S3→[S4]→S0 transition where O2 is formed.
- Asmit Bhowmick
- , Rana Hussein
- & Vittal K. Yachandra
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Article
| Open AccessThe electron–proton bottleneck of photosynthetic oxygen evolution
Microsecond infrared spectroscopy together with quantum chemistry reveal the rate-determining proton and electron movements and identify an oxygen-radical state of the manganese cluster as the S4 state.
- Paul Greife
- , Matthias Schönborn
- & Holger Dau
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Article
| Open AccessVisualizing the disordered nuclear transport machinery in situ
Previously shown as a 60-nm hole in the nuclear pore complex, the transport machinery by FG-nucleoporins is mapped.
- Miao Yu
- , Maziar Heidari
- & Edward A. Lemke
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Article
| Open AccessThe Smc5/6 complex is a DNA loop-extruding motor
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
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| Open AccessCTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion
CTCF is sufficient to block loop extruding cohesin in a DNA tension dependent manner, and induces loop extrusion direction switching and loop shrinkage.
- Iain F. Davidson
- , Roman Barth
- & Jan-Michael Peters
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Structural basis of sensory receptor evolution in octopus
Cryo-electron microscopy analyses reveal adaptations that facilitate the octopus chemotactile receptor’s evolutionary transition from an ancestral role in neurotransmission to detecting greasy environmental agonists for ‘taste by touch’ sensory behaviour.
- Corey A. H. Allard
- , Guipeun Kang
- & Nicholas W. Bellono
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Sensory specializations drive octopus and squid behaviour
Octopus and squid use cephalopod-specific chemotactile receptors to sense their respective marine environments, but structural adaptations in these receptors support the sensation of specific molecules suited to distinct physiological roles.
- Guipeun Kang
- , Corey A. H. Allard
- & Ryan E. Hibbs
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A viral biomolecular condensate coordinates assembly of progeny particles
Phase separation of the human adenovirus 52-kDa protein has an essential role in the formation of biomolecular condensates, regulating the coordinated assembly of viral progeny particles.
- Matthew Charman
- , Nicholas Grams
- & Matthew D. Weitzman
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Article
| Open AccessCFTR function, pathology and pharmacology at single-molecule resolution
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
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Photosynthesis re-wired on the pico-second timescale
By using in vivo ultrafast TA spectroscopy, extraction of electrons directly from photoexcited PSI and PSII in cyanobacterial cells using exogenous electron mediators is demonstrated.
- Tomi K. Baikie
- , Laura T. Wey
- & Jenny Z. Zhang
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Research Briefing |
How an odour molecule activates a human odorant receptor protein
Our sense of smell enables us to perceive a universe of odours. Cryo-electron microscopy has provided an atomic-resolution picture of how an odour molecule is recognized by one of the hundreds of odorant receptors encoded in the human genome, providing a first view into the chemical logic of olfaction.
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Structural basis of odorant recognition by a human odorant receptor
Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.
- Christian B. Billesbølle
- , Claire A. de March
- & Aashish Manglik
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Research Highlight |
Sharpshooter insect flings a flotilla of pee droplets with ease
An insect that subsists on low-energy food has found an efficient way to rid itself of large volumes of waste.
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Phototrophy by antenna-containing rhodopsin pumps in aquatic environments
Light energy transfer from abundant hydroxylated carotenoids to the retinal moiety of widespread light-driven proton pumps is detected.
- Ariel Chazan
- , Ishita Das
- & Oded Béjà
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Structure and thiazide inhibition mechanism of the human Na–Cl cotransporter
Using cryo-electron microscopy, the structures of human Na–Cl cotransporter are determined alone and in complex with a thiazide diuretic.
- Minrui Fan
- , Jianxiu Zhang
- & Liang Feng
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News |
How fingerprints get their one-of-a-kind swirls
The intricate patterns are created during fetal development when fine ridges on the skin form and crash into each other.
- Heidi Ledford
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Article |
Structural insights into the mechanism of the sodium/iodide symporter
Mutations in the sodium/iodide symporter (NIS) cause congenital hypothyroidism, and our results yield insights into how NIS selects, couples and translocates anions, thereby establishing a framework for understanding NIS function.
- Silvia Ravera
- , Juan Pablo Nicola
- & Nancy Carrasco
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Research Briefing |
A proton-pumping enzyme in the brain switches between modes
The enzyme V-ATPase pumps protons into vesicles at the synaptic connections between neuronal cells, and is crucial for neuronal communication. Observations of individual V-ATPase molecules reveal that they randomly switch between proton-pumping, rest and leaking modes, which each last for several minutes, with potential implications for neurotransmission.
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Regulation of the mammalian-brain V-ATPase through ultraslow mode-switching
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
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News Feature |
The shape-shifting blobs that shook up cell biology
More than a decade ago, scientists started finding peculiar droplets inside cells. Now researchers are trying to work out how these ubiquitous beads form and what they do.
- Elie Dolgin
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Article |
Bestrophin-2 and glutamine synthetase form a complex for glutamate release
Electrophysiological, structural and biochemical studies on the bestrophin-2 anion channel reveal asymmetric permeability to glutamate and show that it forms a cooperative machinery in complex with glutamine synthetase for glutamate release.
- Aaron P. Owji
- , Kuai Yu
- & Tingting Yang
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A universal coupling mechanism of respiratory complex I
Cryo-electron microscopy studies of Escherichia coli complex I suggest a conserved mechanism of coupled proton transfers and electrostatic interactions that result in proton ejection from the complex exclusively at the distal NuoL subunit.
- Vladyslav Kravchuk
- , Olga Petrova
- & Leonid Sazanov
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Perspective |
Capillary forces generated by biomolecular condensates
The physical principles of capillarity, including how capillary forces can influence biological processes, are discussed.
- Bernardo Gouveia
- , Yoonji Kim
- & Clifford P. Brangwynne