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| Open AccessActomyosin-dependent formation of the mechanosensitive talin–vinculin complex reinforces actin anchoring
The interaction between focal adhesion proteins vinculin and talin is stimulated by mechanical stretching. Here the authors reconstitute actomyosin-dependent stretching of talin in vitro, and show that the resulting activation of vinculin reinforces anchoring of the adhesion complex to actin.
- Corina Ciobanasu
- , Bruno Faivre
- & Christophe Le Clainche
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Anisotropic energy flow and allosteric ligand binding in albumin
Protein allosteric interactions involve a transfer of structural changes to a remote site. Here, the authors study the relationship between allosteric binding and energy flow, showing how the energy transport mechanism conveys binding energy to remote sites.
- Guifeng Li
- , Donny Magana
- & R. Brian Dyer
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A high-energy-density sugar biobattery based on a synthetic enzymatic pathway
Incomplete oxidation of fuels is a common problem in enzymatic fuel cells and it leads to low energy densities. Zhu et al. report the complete oxidation of sugar in an enzymatic fuel cell through a synthetic enzymatic pathway, which exhibits higher energy densities than lithium-ion batteries.
- Zhiguang Zhu
- , Tsz Kin Tam
- & Y. -H. Percival Zhang
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Optical measurements of long-range protein vibrations
Many biological processes rely on fluctuations in protein structure, but the characterization of extended structural motions is challenging. Here the authors use orientation-sensitive terahertz near-field microscopy to report the optical observation of long-range protein vibrational modes.
- Gheorghe Acbas
- , Katherine A. Niessen
- & A.G. Markelz
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| Open AccessImaging of molecular surface dynamics in brain slices using single-particle tracking
Lateral diffusion of transmembrane signalling molecules is implicated in neuronal communication but imaging in tissue is limited by poor temporal resolution. Here, the authors use quantum dots to label lipids and adhesion molecules, allowing them to track single-molecule motions in subcellular compartments.
- B. Biermann
- , S. Sokoll
- & M. Heine
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Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria
Proteins containing multiple disulphide bonds fold more efficiently if these bonds are formed in a defined order. Koch et al.find that the mitochondrial thiol oxidase Mia40 achieves this by preferentially targeting cysteine residues within a hydrophobic context.
- Johanna R. Koch
- & Franz X. Schmid
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Kinetic modelling indicates that fast-translating codons can coordinate cotranslational protein folding by avoiding misfolded intermediates
The speed of codon translation at the ribosome has a large bearing on the structure of the final protein, with faster rates thought to promote misfolding. Here the authors present a theoretical analysis suggesting that in some cases fast-translating codons may instead improve cotranslational folding.
- Edward P. O’Brien
- , Michele Vendruscolo
- & Christopher M. Dobson
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| Open AccessStructure-based mechanism for Na+/melibiose symport by MelB
The bacterial symporter MelB transports galactosides with Na+, Li+ or H+ ions. Ethayathulla et al. present crystal structures of MelB in two distinct conformations, providing the first structural insights into the transport mechanism of a sodium-coupled permease of the major facilitator superfamily.
- Abdul S. Ethayathulla
- , Mohammad S. Yousef
- & Lan Guan
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Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility
Binding of the Tudor domain of the PHD finger protein PHF1 to H3K36me3 inhibits Polycomb PRC2 complex methyltransferase activity. Here, Musselman et al.characterize this interaction in the context of the full nucleosome and show dual binding of the PHF1 Tudor domain to H3K36me3 and double-stranded DNA.
- Catherine A. Musselman
- , Matthew D. Gibson
- & Tatiana G. Kutateladze
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| Open AccessStructure of a photosynthetic reaction centre determined by serial femtosecond crystallography
Serial femtosecond crystallography is an X-ray free-electron-laser-based method that uses X-ray bursts to determine protein structures. Here the authors present the structure of a photosynthetic reaction centre, an integral membrane protein, achieved with no sign of X-ray-induced radiation damage.
- Linda C. Johansson
- , David Arnlund
- & Richard Neutze
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Functional anatomy of an allosteric protein
ϕ analysis provides a means to tease apart the dynamics of fast conformational changes in proteins by analysing the thermodynamic impact of point mutations. Purohit et al.apply this approach on a grand scale to map energy changes associated with the opening and closing of an acetylcholine receptor.
- Prasad Purohit
- , Shaweta Gupta
- & Anthony Auerbach
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A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors
Bacterial chemoreceptors regulate the kinase CheA via ligand-induced conformational changes. Using long molecular dynamics simulations, Ortega et al.show that these changes are associated with flipping of the stacked aromatic rings of highly conserved phenylalanine residues within the kinase-activating domain.
- Davi R. Ortega
- , Chen Yang
- & Igor B. Zhulin
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Essential regulation of cell bioenergetics in Trypanosoma brucei by the mitochondrial calcium uniporter
The mitochondrial calcium uniporter supports oxidative phosphorylation in mammals; however, it is also present in blood-stage trypanosomes, which lack a functional respiratory chain. Huang et al. show that the mitochondrial calcium uniporter is essential for blood-stage survival and metabolism in Trypanosoma brucei.
- Guozhong Huang
- , Anibal E. Vercesi
- & Roberto Docampo
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| Open AccessMechanisms of molecular transport through the urea channel of Helicobacter pylori
Helicobacter pylori survives in the acidic environment of the stomach by taking up urea and converting it to ammonia and carbon dioxide, which buffer the bacterial periplasm. Using molecular dynamics simulations, McNulty et al. provide insight into the mechanism of urea uptake through the H. pyloriurea transporter.
- Reginald McNulty
- , Jakob P. Ulmschneider
- & Martin B. Ulmschneider
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Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics
Nck1/2 adaptor proteins control the assembly and activity of protein complexes that promote actin polymerization. Buvall et al.show that Nck1 abundance is regulated by the E3 ubiquitin ligase c-Cbl, which competes for Nck binding with the actin-binding protein synaptopodin in podocytes.
- Lisa Buvall
- , Priyanka Rashmi
- & Peter Mundel
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| Open AccessHysteresis of ligand binding in CNGA2 ion channels
Cyclic nucleotide-gated channels mediate olfactory and visual responses. Using a fluorescent cGMP derivative, Nache et al.show that the rate of cyclic nucleotide release from CNGA2 depends on the extent to which this tetrameric receptor is liganded, revealing hysteresis in the gating mechanism.
- Vasilica Nache
- , Thomas Eick
- & Klaus Benndorf
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| Open AccessSecondary anionic phospholipid binding site and gating mechanism in Kir2.1 inward rectifier channels
Inwardly rectifying potassium channels require interactions with both PI(4,5)P2 and a second anionic phospholipid for full activation. Lee et al. locate the secondary anionic phospholipid-binding site in Kir2.1 and reveal how it synergistically promotes PI(4,5)P2sensitivity.
- Sun-Joo Lee
- , Shizhen Wang
- & Colin G. Nichols
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Characterization and modelling of interspecies electron transfer mechanisms and microbial community dynamics of a syntrophic association
Microbial community function depends on metabolic interdependencies between individual species, some of which include electron transfer. Nagarajan et al. use genomic, transcriptomic and modelling approaches to describe the mechanisms supporting the syntrophic relationship between Geobacter metallireducens and Geobacter sulfurreducens.
- Harish Nagarajan
- , Mallory Embree
- & Karsten Zengler
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From protein sequence to dynamics and disorder with DynaMine
Predicting the dynamics and disorder of a protein is a computationally complex task that, until now, has depended on prior knowledge of protein structure. Cilia et al.develop a tool to rapidly predict protein backbone dynamics based on sequence alone.
- Elisa Cilia
- , Rita Pancsa
- & Wim F. Vranken
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Equilibrium selectivity alone does not create K+-selective ion conduction in K+ channels
The preference of potassium channels to bind K+ ions over Na+ ions at equilibrium has been proposed to determine their exclusive K+ conductance. Liu and Lockless show that a related, non-selective cation channel also binds only K+ions at equilibrium, suggesting that this property alone does not determine selectivity.
- Shian Liu
- & Steve W. Lockless
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| Open AccessSodium and potassium competition in potassium-selective and non-selective channels
K+ channels are selective for K+ despite the fact that Na+ can bind and conduct through the selectivity filter. Sauer et al. show that a K+-selective NaK2K channel has two high-affinity K+-binding sites, whereas a non-selective NaK2CNG channel has one, and propose a double-barrier mechanism for ion selectivity.
- David B. Sauer
- , Weizhong Zeng
- & Youxing Jiang
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Probing single- to multi-cell level charge transport in Geobacter sulfurreducens DL-1
Microbial fuels cells present a way of generating electricity using the natural metabolism of microorganisms. Here the authors carry out single-cell current measurements ofGeobacter sulfurreducensDL-1 to determine the upper limits of microbial fuel cell performance.
- Xiaocheng Jiang
- , Jinsong Hu
- & Justin C. Biffinger
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Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain
Regulator of K+ conductance (RCK) domains control the gating of potassium channels in response to ligands such as calcium. Smith et al. solve structures of the MthK RCK domain with varying numbers of calcium ions bound, and reveal the structural basis of allosteric coupling between calcium binding sites.
- Frank J. Smith
- , Victor P.T. Pau
- & Brad S. Rothberg
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Torque modulates nucleosome stability and facilitates H2A/H2B dimer loss
Histone H2A-H2B heterodimers are lost from nucleosomes during transcription by RNA polymerase II. Here Sheinin et al. investigate the behaviour of single nucleosomes subjected to DNA supercoiling and observe a loss of these heterodimers under positive supercoiling, which might have implications for histone turnover during transcription in vivo.
- Maxim Y. Sheinin
- , Ming Li
- & Michelle D. Wang
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Article
| Open AccessStructural and functional characterization of two alpha-synuclein strains
α-synuclein is implicated in neurodegenerative diseases. Bousset et al. generate two α-synuclein polymorphs and find differences in aggregation, function and toxicity, suggesting that these altered properties may be the cause for differences in disease progression.
- Luc Bousset
- , Laura Pieri
- & Ronald Melki
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| Open AccessTargeted delivery of colloids by swimming bacteria
Transport of colloidal cargoes to target sites can be done by controlling active carriers, like self-propelled bacteria, under external stimuli. Koumakis et al.show that bacteria can autonomously achieve the same goal when moving over pre-designed asymmetric microstructures.
- N. Koumakis
- , A. Lepore
- & R. Di Leonardo
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Molecular determinants of common gating of a ClC chloride channel
The ClC family of chloride channels are homodimeric and contain two pores that are gated simultaneously. Bennetts and Parker combine homology modelling and mutant-cycle analysis to reveal structural linkages important for coordination of gating between subunits.
- Brett Bennetts
- & Michael W. Parker
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| Open AccessRole of the C-terminal domain in the structure and function of tetrameric sodium channels
Prokaryotic voltage-gated sodium channels possess dynamically disordered cytoplasmic C-terminal domains. Bagnéris et al. present the structure of the Magnetococcus marinusNavMs pore and C-terminal domain and reveal its role in coupling channel inactivation and opening.
- Claire Bagnéris
- , Paul G. DeCaen
- & B. A. Wallace
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| Open AccessA nanopore machine promotes the vectorial transport of DNA across membranes
Transport of DNA molecules across lipid membranes requires protein conduits such as the nuclear pore complex. Franceschiniet al.engineer an artificial sequence-selective DNA transporter by attaching gating oligonucleotides to a bacterial nanopore.
- Lorenzo Franceschini
- , Misha Soskine
- & Giovanni Maglia
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High-resolution three-dimensional mapping of mRNA export through the nuclear pore
Messenger RNAs and their associated proteins are transported from the nucleus through highly selective nuclear pore complexes. Using ultrahigh resolution single-molecule imaging, the authors visualise the path taken by each messenger RNA as it negotiates the pore’s selectivity filter.
- Jiong Ma
- , Zhen Liu
- & Weidong Yang
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Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel
TMEM16-channel family members have been shown to be involved in Ca2+-dependent lipid scrambling, but whether they have intrinsic scramblase activity remains controversial. Malvezzi et al. identify a TMEM16 family member in Aspergillus in which a single Ca2+-binding site regulates intrinsic channel and scramblase activities.
- Mattia Malvezzi
- , Madhavan Chalat
- & Alessio Accardi
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Srs2 prevents Rad51 filament formation by repetitive motion on DNA
Srs2 is a DNA helicase and single-stranded DNA translocase that prevents homologous recombination by dismantling Rad51 filaments. Qiu et al.use single-molecule techniques to describe Rad51 filament formation and show that Srs2 displays repetitive activity on single-stranded DNA, which prevents re-formation of Rad51 filaments after dismantling.
- Yupeng Qiu
- , Edwin Antony
- & Sua Myong
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The unusual dynamics of parasite actin result from isodesmic polymerization
Actin normally polymerizes into filaments in a cooperative manner, with nucleation and elongation phases. Skillman et al. show that actin from the protozoan parasite Toxoplasma gondiipolymerizes in an isodesmic manner, without any evidence of nucleation, resulting in filaments that are very short and unstable.
- Kristen M. Skillman
- , Christopher I. Ma
- & L. David Sibley
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Synthetic polyamines promote rapid lamellipodial growth by regulating actin dynamics
While small molecules that destabilize actin filaments are readily available, artificially stimulating actin polymerization in cells typically involves genetic manipulation. Here, the authors design cell-permeable branched polyamines that promote lamellipodium formation by stimulating actin polymerization.
- Iliana Nedeva
- , Girish Koripelly
- & Daniel Riveline
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Turbulence drives microscale patches of motile phytoplankton
Patchiness in the distribution of phytoplankton promotes many of the ecological interactions that underpin the marine food web. This study shows that turbulence, ubiquitous in the ocean, counter-intuitively ‘unmixes’ a population of motile phytoplankton, generating intense, small-scale patchiness in its distribution.
- William M. Durham
- , Eric Climent
- & Roman Stocker
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Selectivity mechanism of the mechanosensitive channel MscS revealed by probing channel subconducting states
The E. colimechanosensitive channel MscS responds to hypoosmotic swelling by opening a weakly anion-selective pore. Here, the authors report that the structural determinants of this selectivity are located not in the pore, but in the large water-filled cytoplasmic domain.
- C. D. Cox
- , T. Nomura
- & B. Martinac
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Far-red light photoactivatable near-infrared fluorescent proteins engineered from a bacterial phytochrome
Near-infrared fluorescent proteins have applications in deep-tissue and whole-body imaging. Here, the authors report photoactivatable near-infrared proteins engineered from bacteria, with substantial contrast enhancement, which may be advantageous for in vivoimaging in high autofluorescence conditions.
- Kiryl D. Piatkevich
- , Fedor V. Subach
- & Vladislav V. Verkhusha
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| Open AccessConformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertion
The fidelity of DNA polymerases depends on conformational changes that promote the rejection of incorrect nucleotides. Here, by using an intramolecular single-molecule FRET assay, the authors establish and characterize the partially closed conformation as a crucial fidelity checkpoint.
- Johannes Hohlbein
- , Louise Aigrain
- & Achillefs N. Kapanidis
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| Open AccessThe thermodynamic patterns of eukaryotic genes suggest a mechanism for intron–exon recognition
The thermodynamics of unwinding polynucleotide duplexes can be determined from energy changes for DNA and mRNA interactions. Here the authors show that the ratio between mRNA/DNA and DNA/DNA duplex stability upstream of the 3′- spice sites is a characteristic that can contribute to intron–exon recognition.
- Marina N. Nedelcheva-Veleva
- , Mihail Sarov
- & Stoyno S. Stoynov
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Stimulated emission depletion-based raster image correlation spectroscopy reveals biomolecular dynamics in live cells
RICS is a fluorescence imaging technique used to reveal fast molecular dynamics inside living cells and tissues. Hedde et al.combine RICS with super-resolution STED microscopy (STED-RICS) to achieve an enhanced multiplexing capability and to extend the range of usable fluorophore concentrations.
- Per Niklas Hedde
- , René M. Dörlich
- & G. Ulrich Nienhaus
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| Open AccessDynamics and stoichiometry of a regulated enhancer-binding protein in live Escherichia coli cells
Cellular adaptive responses require temporal and spatial control of key regulatory protein complexes. Mehta et al. describe the dynamic interaction of a transcriptional activator mediating membrane stress response in E. coliwith its negative regulator, the cell membrane and the transcription machinery.
- Parul Mehta
- , Goran Jovanovic
- & Martin Buck
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| Open AccessCyclic electron flow is redox-controlled but independent of state transition
The switch from linear to cyclic electron flow has long been thought to rely on the migration of antenna proteins from Photosystem II to Photosystem I. Takahashi et al. report that this is not the case and that cyclic electron flow is tuned by the intrachloroplastic redox power.
- Hiroko Takahashi
- , Sophie Clowez
- & Fabrice Rappaport
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Dynamics of 5-hydroxymethylcytosine during mouse spermatogenesis
Changes in DNA methylation during mammalian spermatogenesis are poorly understood. The authors show that the content of 5-hydroxymethylcytosine, a stable intermediate of DNA demethylation, changes dynamically during mouse spermatogenesis and is associated with functional genomic regions and transcription.
- Haiyun Gan
- , Lu Wen
- & Fuchou Tang
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Mechanistic and environmental control of the prevalence and lifetime of amyloid oligomers
Amyloid fibrils are implicated in a number of diseases but the origin of their length distributions is poorly understood. Here, evidence is presented to support a structural transition at a critical mass concentration, above which fragmentation of fibrils is suppressed.
- Ryan J. Morris
- , Kym Eden
- & Cait E. MacPhee
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Article
| Open AccessThe pore of voltage-gated potassium ion channels is strained when closed
Voltage-gated potassium channels open and close in response to changes in transmembrane potential, but their opening mechanism is poorly understood. Here, free energy molecular dynamics simulations show that strain accumulates as the pore closes, which subsequently drives opening.
- Philip W. Fowler
- & Mark S. P. Sansom
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Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels
Dehydrated hereditary stomatocytosis is a genetic condition in which the permeability of red blood cells to cations in increased. Albuisson and colleagues find that mutations in the mechanically-activated PIEZO1 ion channel are the major cause of the disease and result in more slowly inactivating currents.
- Juliette Albuisson
- , Swetha E Murthy
- & Ardem Patapoutian
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Formin mDia1 senses and generates mechanical forces on actin filaments
Formins are a family of protein complexes that accelerate actin filament nucleation and elongation. Jegou et al.show that the formin mDia1 can generate mechanical tension in actin filaments, while conversely, pulling forces applied by viscous drag increase formin elongation activity.
- Antoine Jégou
- , Marie-France Carlier
- & Guillaume Romet-Lemonne
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Transcription factor binding kinetics constrain noise suppression via negative feedback
Live cell imaging have recently revealed that transcription factors spend up to 4 min to find and bind their chromosomal binding site. Grönlund et al. show that this slow search process leads to tradeoffs between strength and speed of negative autoregulation for effective noise suppression.
- Andreas Grönlund
- , Per Lötstedt
- & Johan Elf
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| Open AccessALKBH4-dependent demethylation of actin regulates actomyosin dynamics
The division of a single eukaryotic cell into two requires actomyosin-dependent contraction. Here the authors show that lysine methylation of actin inhibits contractility during cytokinesis by blocking its association with myosin, and this modification is reversed at the contractile ring by the demethylase ALKBH4.
- Ming-Ming Li
- , Anja Nilsen
- & Yun-Gui Yang