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| Open AccessA novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel
Voltage-gated potassium channels cycle between closed and open states through poorly-defined transitions. Pless and colleagues incorporate artificial amino acids into Shaker potassium channels and find that that the negative electrostatic surface potential of Phe481, destabilizes the channel open state.
- Stephan A. Pless
- , Ana P. Niciforovic
- & Christopher A. Ahern
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Article
| Open AccessAtALMT9 is a malate-activated vacuolar chloride channel required for stomatal opening in Arabidopsis
Aluminium-activated malate transporters are exclusive to plants, regulating the transport of ions across the membranes on which they are expressed. De Angeli and colleagues show that AtALMT9 acts as a vacuolar chloride channel that is activated by cytosolic malate, and that this regulates stomata aperture.
- Alexis De Angeli
- , Jingbo Zhang
- & Enrico Martinoia
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Article
| Open AccessAuto-production of biosurfactants reverses the coffee ring effect in a bacterial system
The coffee ring effect is commonly observed in drying droplets containing suspended matter leading to a deposition at the droplet edge. Sempels et al. show that self-generated biosurfactants in living bacterial systems reverse the coffee ring effect and result in a homogeneous deposition.
- Wouter Sempels
- , Raf De Dier
- & Jan Vermant
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Article
| Open AccessThe four-transmembrane protein IP39 of Euglena forms strands by a trimeric unit repeat
IP39 is an abundant protozoan protein known to form highly-ordered striations in Euglena gracilis’ plasma membrane. Here, Suzuki et al. determine its three-dimensional structure by electron crystallography revealing that IP39 polymerises to form trimeric longitudinal units arranged in a molecular strand of antiparallel double-rows.
- Hiroshi Suzuki
- , Yasuyuki Ito
- & Sachiko Tsukita
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The function of fin rays as proprioceptive sensors in fish
Electrophysiological studies in some fish species suggest that proprioception is needed for fin movement. Here the authors test mechanosensory abilities of afferent nerves in pectoral fin rays, and find that the activity of fin ray nerve fibres reflects the amplitude and velocity of fin ray bending.
- Richard Williams IV
- , Nicole Neubarth
- & Melina E. Hale
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Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel
Alcohols and anaesthetics exert their effects by potentiating ligand-gated ion channels. Here, the authors determine crystal structures of a bacterial ligand-gated ion channel in the presence of alcohols and anaesthetics, and describe a structural mechanism for stabilization of the open form of the channel.
- Ludovic Sauguet
- , Rebecca J. Howard
- & Marc Delarue
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Article
| Open AccessMolecular mechanics of mineralized collagen fibrils in bone
Bone is a natural composite of collagen and hydroxyapatite but, surprising, little is known about its characteristics at the molecular scale. Nair et al. conduct molecular-scale simulations of mineralized collagen networks to better understand how bone achieves superior mechanical properties to its constituents.
- Arun K. Nair
- , Alfonso Gautieri
- & Markus J. Buehler
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| Open AccessMechanical unzipping and rezipping of a single SNARE complex reveals hysteresis as a force-generating mechanism
Interactions between (SNARE) proteins on vesicle and target membranes provide the force necessary to drive membrane fusion. By applying piconewton forces to single SNARE complexes, the authors identify a partially assembled intermediate state that reveals how force is generated in a consistent direction.
- Duyoung Min
- , Kipom Kim
- & Tae-Young Yoon
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Dynamic switching of calmodulin interactions underlies Ca2+ regulation of CaV1.3 channels
Calmodulin regulation of Ca2+ channels is an important Ca2+-feedback system. The structural underpinnings of this modulation are unclear, but this study reports the molecular states underlying channel regulation.
- Manu Ben Johny
- , Philemon S. Yang
- & David T. Yue
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Energetics of activation of GTP hydrolysis on the ribosome
Ribosomal protein synthesis is driven by the hydrolysis of GTP. Wallin and colleagues employ molecular dynamics and computer simulations to show that a universally conserved histidine promotes GTP hydrolysis in its protonated form, and is driven into the active conformation by interactions with the ribosome.
- Göran Wallin
- , Shina C. L. Kamerlin
- & Johan Åqvist
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A light-driven sodium ion pump in marine bacteria
Light-driven proton-pumping rhodopsins are widely distributed in microorganisms and convert sunlight energy into proton gradients. Inoue et al. report the discovery of a light-driven sodium ion pump from marine bacteria.
- Keiichi Inoue
- , Hikaru Ono
- & Hideki Kandori
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Evidence for a material gradient in the adhesive tarsal setae of the ladybird beetle Coccinella septempunctata
Many insects cling to surfaces by means of specific bristles on the tips of their legs. Peisker et al. show that in the beetle Coccinella septempunctatathe composition and stiffness of these bristles vary dramatically along their length, likely allowing for a better grip to uneven surfaces.
- Henrik Peisker
- , Jan Michels
- & Stanislav N. Gorb
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Biased Brownian stepping rotation of FoF1-ATP synthase driven by proton motive force
The visualization of ion-motive-force driven conformational dynamics of membrane proteins is hampered by technical difficulties. Here, the authors develop an experimental platform to visualize the rotary dynamics of ATP synthase driven by proton-motive-force.
- Rikiya Watanabe
- , Kazuhito V. Tabata
- & Hiroyuki Noji
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Probing transcription factor diffusion dynamics in the living mammalian embryo with photoactivatable fluorescence correlation spectroscopy
Transcription factor diffusion along DNA regulates many fundamental cellular and developmental processes. Kaur et al. combine photoactivation and fluorescence correlation spectroscopy to investigate transcription factor diffusion in mouse embryos and show that diffusion kinetics change during cell differentiation.
- Gurpreet Kaur
- , Mauro W. Costa
- & Nicolas Plachta
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CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire
Cullin 1-RING ubiquitin ligase complexes interact with a wide variety of substrates by recruiting different substrate receptor subunits. Here the authors demonstrate that CAND1 promotes rapid exchange of substrate receptors, thus ensuring comprehensive sampling of the entire repertoire.
- Shuangding Wu
- , Wenhong Zhu
- & Dieter A. Wolf
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Impact of macromolecular crowding on DNA replication
Macromolecular crowding significantly affects interactions between macromolecules such as proteins, DNA and RNA. Akabayov and colleagues use a SAXS reconstitution assay to show that the effect of macromolecular crowding on T7 DNA replication causes structural changes of the replisome.
- Barak Akabayov
- , Sabine R. Akabayov
- & Charles C. Richardson
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Human haemodynamic frequency harmonics regulate the inflammatory phenotype of vascular endothelial cells
Natural variations in blood flow haemodynamics are associated with localized inflammation and atherosclerosis. Here the authors show that individual harmonics present within this complex signal have distinct impacts on the inflammatory phenotype in endothelial cells.
- Ryan E. Feaver
- , Bradley D. Gelfand
- & Brett R. Blackman
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Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45/CASQ1 double knockout mice
Calcium influx through the Cav1.1 channel initiates skeletal muscle contractions. Zorzato and colleagues report a role for the proteins JP45 and calsequestrin in strengthening skeletal muscle contraction by modulating Cav1.1 channel activity.
- Barbara Mosca
- , Osvaldo Delbono
- & Francesco Zorzato
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Article
| Open AccessReal-time single-molecule co-immunoprecipitation analyses reveal cancer-specific Ras signalling dynamics
Co-immunoprecipitation provides static and qualitative information about protein–protein interactions. Lee et al.create real-time movies of single protein–protein interactions during co-immunoprecipitation, and use them to assess the dynamics of mutant Ras proteins derived from tumours.
- Hong-Won Lee
- , Taeyoon Kyung
- & Tae-Young Yoon
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| Open AccessDisease mutations in the ryanodine receptor N-terminal region couple to a mobile intersubunit interface
Ryanodine receptors are calcium-release channels located in the membrane of the sarcoplasmic and endoplasmic reticulum. Kimlicka et al.compare pseudo-atomic models of the N-terminal area in the open and closed states and characterize the mutations in the N-terminal that disrupt channel opening.
- Lynn Kimlicka
- , Kelvin Lau
- & Filip Van Petegem
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Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)
The bacterial tetracycline resistance protein Tet(O) binds to the ribosome, preventing tetracycline from inhibiting translation. Using cryo-electron microscopic reconstruction, the authors present an atomic model of Tet(O) bound to the 70S ribosome, and reveal how Tet(O) promotes antibiotic resistance.
- Wen Li
- , Gemma C. Atkinson
- & Joachim Frank
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Article
| Open AccessInterplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations
Dendritic cells use protrusive structures called podosomes to probe the extracellular environment. Here the authors reveal how interplay between actin-mediated core growth and myosin-mediated tension regulates podosome protrusion.
- K. van den Dries
- , M.B.M Meddens
- & A. Cambi
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Non-uniform membrane diffusion enables steady-state cell polarization via vesicular trafficking
The mechanism by which proteins become polarized to a specific cortical site in budding yeast cells has been a topic of recent debate. Slaughter et al.show that differing diffusion rates of Cdc42 within plasma membrane environments sustain the polarized state.
- Brian D. Slaughter
- , Jay R. Unruh
- & Rong Li
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Evolution of the protein stoichiometry in the L12 stalk of bacterial and organellar ribosomes
The ribosomal stalk L12 is the only multi-copy protein in the ribosome and is essential for translation. Here Davydov et al.use a bioinformatics and mass spectrometry approach to study the evolution of L12 in bacterial ribosomes and predict its stoichiometry in a wide range of species.
- Iakov I. Davydov
- , Ingo Wohlgemuth
- & Marina V. Rodnina
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| Open AccessMultiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel
In outwardly rectifying potassium channels, depolarization initiates conformational changes in voltage-sensing domains. Goldschen-Ohmet al. find that movement of three specific domains correlates with conductance levels, and rearrangements of a fourth domain results in preinactivation subconductance states.
- Marcel P. Goldschen-Ohm
- , Deborah L. Capes
- & Baron Chanda
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Article
| Open AccessStructural insights into protein-only RNase P complexed with tRNA
RNase P is a key enzyme implicated in transfer RNA maturation that removes the 5′-leader sequences from transfer RNA precursors. In this study, a biophysical characterization of a novel protein-only variant of RNase P, known as PRORP (PROteinaceous RNase P), reveals that transfer RNA recognition by PRORP is similar to that by ribonucleoprotein RNase P.
- Anthony Gobert
- , Franziska Pinker
- & Philippe Giegé
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Article
| Open AccessAlba shapes the archaeal genome using a delicate balance of bridging and stiffening the DNA
How the genome is physically organized is less understood in archaea than in eubacteria or eukaryotes. Laurens et al. measure DNA binding by the Sulfolobus solfataricusproteins Alba1 and Alba2 using single-molecule techniques and conclude that the presence of Alba2 leads to more bridging between DNA.
- Niels Laurens
- , Rosalie P.C. Driessen
- & Gijs J.L. Wuite
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Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex
Polycystic kidney disease family proteins form heteromeric complexes with transient receptor potential channel subunits of the TRPP subfamily. Yu and colleagues find that the polycystic kidney disease protein, PKD1L3, is an ion channel pore-forming subunit in the acid-sensing PKD1L3/TRPP3 complex.
- Yong Yu
- , Maximilian H. Ulbrich
- & Jian Yang
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Sub-resolution lipid domains exist in the plasma membrane and regulate protein diffusion and distribution
The plasma membrane is thought to comprise a patchwork of ordered and disordered microdomains; however, direct evidence for this in intact cells remains elusive. Using unmixing of fluorescence lifetime decays, Owen et al. show that ordered domains occupy a majority of the plasma membrane surface in living cells.
- Dylan M. Owen
- , David J. Williamson
- & Katharina Gaus
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| Open AccessLocalizing internal friction along the reaction coordinate of protein folding by combining ensemble and single-molecule fluorescence spectroscopy
Internal friction affects the kinetics of protein folding. Borgiaet al. investigate how this friction affects the folding dynamics of the protein spectrin, revealing a potential role in the rate-limiting conformational changes.
- Alessandro Borgia
- , Beth G. Wensley
- & Benjamin Schuler
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Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel
Mutations of the NaV1.7 voltage-gated sodium channel are implicated in abnormal pain signal transduction. Yang and colleagues perform structural modeling, mutant cycle analysis and electrophysiology on specific mutants and find that they can accurately predict their response profiles to channel blockers.
- Yang Yang
- , Sulayman D. Dib-Hajj
- & Stephen G. Waxman
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Imaging the post-fusion release and capture of a vesicle membrane protein
Rapid synaptic transmission requires efficient recycling of synaptic vesicle membrane proteins. Sochackiet al.use live cell, electron and super-resolution microscopy to visualize exocytosis of vesicular transporters and their rapid recapture in clathrin-rich microdomains in the plasma membrane.
- Kem A. Sochacki
- , Ben T. Larson
- & Justin W. Taraska
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Cobweb-weaving spiders produce different attachment discs for locomotion and prey capture
Spider webs consist of scaffolding silk, which supports the cobweb, and gumfoot silk, which can detach easily from the web upon contact with prey. Here, these different mechanical demands are shown to be met by silk attachments of two distinct architectures using the same pyriform silk secretions.
- Vasav Sahni
- , Jared Harris
- & Ali Dhinojwala
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Article
| Open AccessStructure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing
Sodium-gated ion channels open and close in response to the flow of ions. Here, McCusker et al.report the open structure of a sodium-gated ion channel pore from a bacterial homologue, and show, by comparison with the closed structure, that the movement of a C-terminal helix is sufficient to open the channel.
- Emily C. McCusker
- , Claire Bagnéris
- & B.A. Wallace
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Sound-induced length changes in outer hair cell stereocilia
In the inner ear, sound waves produce movements in hair cell sterocilia, triggering the opening of ion channels. Hakizimana and colleagues show that the resultant currents change the length of sterocilia, and that these length changes alter the efficiency by which sound is converted into electrical signals.
- Pierre Hakizimana
- , William E. Brownell
- & Anders Fridberger
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| Open AccessEfficacy of the β2-adrenergic receptor is determined by conformational equilibrium in the transmembrane region
Many drugs exist that target the β-adrenergic receptor, but they have different efficacies. Kofukuet al. use NMR to show that methionine 82 in the transmembrane domain undergoes conformational changes depending on whether agonists or inverse agonists are bound, explaining the differential drug efficacy.
- Yutaka Kofuku
- , Takumi Ueda
- & Ichio Shimada
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Article
| Open AccessThe allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling
Class A seven transmembrane helical receptors harbour vestibules at the entrance to the ligand-binding domain. Here, Bocket al. use probes to monitor the conformation of the M2 muscarinic receptor and show that the vestibule alters the extent of receptor movement.
- Andreas Bock
- , Nicole Merten
- & Klaus Mohr
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Rotational dynamics of cargos at pauses during axonal transport
Vesicle trafficking in the cell is likely to involve a tug-of-war between motor proteins of opposing directionality. Guet al. use high-speed single-particle tracking in neurons to uncover rotation of paused cargo vesicles, providing insight into the changing forces as the vesicles change direction.
- Yan Gu
- , Wei Sun
- & Ning Fang
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| Open AccessControlled rotation of the F1-ATPase reveals differential and continuous binding changes for ATP synthesis
Reverse rotation of the F1-ATPase results in the synthesis, rather than hydrolysis of ATP. Adachiet al. show that the molecular mechanism of ATP synthesis is the reverse of hydrolysis-driven rotation of the motor, and that ADP and ATP are discriminated by angle-dependent binding.
- Kengo Adachi
- , Kazuhiro Oiwa
- & Kazuhiko Kinosita Jr
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Imaging enzyme-triggered self-assembly of small molecules inside live cells
Supramolecular interactions allow some small molecules to self-assemble into nanofibres and hydrogels in aqueous environments. Gaoet al.report a hydrogelator that forms fluorescent nanofibres within cells, leading to the visualization of their self-assembly at the endoplasmic reticulum.
- Yuan Gao
- , Junfeng Shi
- & Bing Xu
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Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A
The mitochondrial transcription factor A (TFAM) mediates both mitochondrial transcription and DNA compaction, but how it achieves these two functions is unknown. In this study, TFAM is shown to slide along DNA and cause local melting, suggesting a mechanism for how TFAM modulates both transcription and compaction.
- Géraldine Farge
- , Niels Laurens
- & Gijs J.L. Wuite
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Article
| Open AccessDistant residues mediate picomolar binding affinity of a protein cofactor
Flavodoxin requires tight binding of its FMN cofactor to be active, but the residues involved are unknown. In this biophysical study, FMN binding is shown to change from nanomolar to picomolar affinity on extremely slow protein relaxation and the residues responsible for cofactor binding are identified.
- Yves J.M. Bollen
- , Adrie H. Westphal
- & Carlo P.M. van Mierlo
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Evidence for activity-regulated hormone-binding cooperativity across glycoprotein hormone receptor homomers
Glycoprotein hormone receptors show negative cooperativity following a single molecule of agonist binding to each receptor dimer. Here, constitutively active receptors are shown to display less cooperative allosteric regulation, suggesting a direct relationship between conformational changes in the transmembrane domain and allosteric behaviour of the receptor dimers.
- Maxime Zoenen
- , Eneko Urizar
- & Sabine Costagliola
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TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export
The TREX complex and Nxf1 are involved in the export of mRNA from the nucleus but the precise molecular function of TREX is unclear. Here, the TREX components Aly and Thoc5 are shown to bind to Nxf1 resulting in a change in Nxf1 conformation that permits binding to mRNA and nuclear export.
- Nicolas Viphakone
- , Guillaume M. Hautbergue
- & Stuart A. Wilson
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Mechanism of resilin elasticity
Resilin is a polymeric elastic protein that is important for the flight and jumping of insects. Here, the structure-function relationships ofDrosophilaresilin are investigated, and a mechanical model is proposed to account for its elasticity.
- Guokui Qin
- , Xiao Hu
- & David L. Kaplan
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Controlled delivery of bioactive molecules into live cells using the bacterial mechanosensitive channel MscL
The bacterial channel protein MscL opens in response to mechanical forces and could be exploited for vesicular-based drug delivery. Doerneret al. show that functional MscL can be expressed in mammalian cells and facilitate the controlled cellular uptake of relatively large, membrane-impermeable bioactive molecules.
- Julia F. Doerner
- , Sebastien Febvay
- & David E. Clapham
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Article
| Open AccessDistinct loops in arrestin differentially regulate ligand binding within the GPCR opsin
Following retinalcis/trans isomerisation, the active form of the G-protein-coupled receptor rhodopsin decays to opsin and all-trans-retinal. In this study, arrestin, a regulator of G-protein-coupled receptor activity, is shown to facilitate the concurrent sequestering of toxic all-trans-retinal and regeneration of 11-cis-retinal within the opsin population.
- Martha E. Sommer
- , Klaus Peter Hofmann
- & Martin Heck
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Gating of cyclic nucleotide-gated channels is voltage dependent
Cyclic nucleotide-gated channels are apparently voltage insensitive despite having the S4-type voltage sensor. Marchesiet al.show that the gating of wild-type CNGA1 and native CNG channels is voltage-independent in the presence of Li+, Na+ and K+, but that it is voltage-dependent in the presence of Rb+, Cs+ and organic cations.
- Arin Marchesi
- , Monica Mazzolini
- & Vincent Torre
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Article
| Open AccessSwitching of myosin-V motion between the lever-arm swing and Brownian search-and-catch
The motor protein myosin-V transports cargo along actin filaments, but the biophysical mechanisms by which myosin-V generates force are unclear. Here, optical tweezers and a DNA handle are used to study the forces generated by myosin-V: the mechanism of force generation is found to depend on the load applied.
- Keisuke Fujita
- , Mitsuhiro Iwaki
- & Toshio Yanagida