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| Open AccessPrimary cell wall inspired micro containers as a step towards a synthetic plant cell
Assembling synthetic plant cell is difficult due to the presence of primary cell wall. Here, the authors describe the assembly of lipid-containing bodies that can be coated with cellulose and pectin, and show how these so-called plantosomes can be manipulated by changing surrounding milieu.
- T. Paulraj
- , S. Wennmalm
- & A. J. Svagan
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Article
| Open AccessThe Ca2+ permeation mechanism of the ryanodine receptor revealed by a multi-site ion model
Although the permeation mechanisms for K+ and Na+ channels have been extensively studied, the ion permeation mechanism through Ca2+ channels was largely unknown. Here the authors develop a multisite Ca2+ model that can be used in the framework of classical MD simulations to study Ca2+ in a quantitative manner, and use it to investigate the ion permeation mechanism of the ryanodine receptor 1.
- Aihua Zhang
- , Hua Yu
- & Chen Song
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Article
| Open AccessWhole-cell imaging of plasma membrane receptors by 3D lattice light-sheet dSTORM
The organisation of plasma membrane receptors is important for their function. Here the authors combine lattice light-sheet microscopy with 3D single-molecule localisation microscopy (dSTORM) and single-particle tracking to study the distribution and motility of several surface receptors.
- Felix Wäldchen
- , Jan Schlegel
- & Markus Sauer
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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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Article
| Open AccessHierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases
The mussel byssus cuticle is a wear-resistant and extensible metalloprotein composite. Here, the authors probed the cuticle nanostructure and composition before, during and after fabrication revealing a crucial role of metal-binding proteins that self-organize via liquid-liquid phase separation.
- Franziska Jehle
- , Elena Macías-Sánchez
- & Matthew J. Harrington
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Article
| Open AccessTripartite phase separation of two signal effectors with vesicles priming B cell responsiveness
Antibody-mediated immune responses rely on antigen recognition by the B cell antigen receptor (BCR) and SLP65 is a key scaffold protein mediating BCR signaling. Here authors show that effective B cell activation requires tripartite phase separation of SLP65, CIN85, and lipid vesicles.
- Leo E. Wong
- , Arshiya Bhatt
- & Christian Griesinger
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Article
| Open AccessOuter membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface
The O-antigen of LPS is known to limit the binding of antibody to bacterial surface antigens. Here the AUs show that the chemical and physical structure of the O-antigen are central factors in limiting the exposure of surface antigens to antibodies during Salmonella infection, thus defining their protective qualities.
- C. Coral Domínguez-Medina
- , Marisol Pérez-Toledo
- & Adam F. Cunningham
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Article
| Open AccessMinimally disruptive optical control of protein tyrosine phosphatase 1B
Protein tyrosine phosphatases regulate many cellular processes but are difficult to study in their native context. Here the authors develop an approach for using light to control the activity of a disease-relevant phosphatase without interfering with its native cellular organization.
- Akarawin Hongdusit
- , Peter H. Zwart
- & Jerome M. Fox
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Article
| Open AccessRegulation of lipid saturation without sensing membrane fluidity
Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. Here authors reconstituted the core machinery for regulating lipid saturation in baker’s yeast to directly characterize its response to defined membrane environments and uncover its mode-of-action.
- Stephanie Ballweg
- , Erdinc Sezgin
- & Robert Ernst
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Article
| Open AccessTwo-stage electro–mechanical coupling of a KV channel in voltage-dependent activation
In voltage-gated potassium (KV) channels, the voltage-sensing domain (VSD) undergoes activation states to trigger pore opening via electro–mechanical (E–M) coupling. Here authors show that KV7.1 undergoes a two-stage E–M coupling mechanism during voltage-dependent activation.
- Panpan Hou
- , Po Wei Kang
- & Jianmin Cui
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Article
| Open AccessConformational plasticity of ligand-bound and ternary GPCR complexes studied by 19F NMR of the β1-adrenergic receptor
The β1-adrenergic receptor (β1AR) is a G-protein-coupled receptor (GPCRs) that binds catecholamine ligands. Here the authors employ site-specific labelling and 19F NMR measurements to characterise the structural changes and dynamics in the cytoplasmic region of β1AR upon agonist stimulation and coupling to a Gs-protein-mimetic nanobody.
- J. Niclas Frei
- , Richard W. Broadhurst
- & Daniel Nietlispach
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Article
| Open AccessStructural basis of proton-coupled potassium transport in the KUP family
KUP transporters facilitate potassium uptake by the co-transport of protons and are key players in potassium homeostasis. Here authors identify the potassium importer KimA from Bacillus subtilis as a new member of the KUP transporter family and show the cryo-EM structure of KimA in an inward-occluded, trans-inhibited conformation.
- Igor Tascón
- , Joana S. Sousa
- & Inga Hänelt
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Article
| Open AccessCharge transfer from the carotenoid can quench chlorophyll excitation in antenna complexes of plants
The plant photosynthetic machinery quenches excess excitation energy to avoid photodamage. Here, via molecular dynamics and quantum chemical calculations, Cupellini et al. show that lutein/chlorophyll pairs in light-harvesting complex II can quench excess energy via a transient charge transfer state.
- Lorenzo Cupellini
- , Dario Calvani
- & Benedetta Mennucci
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Article
| Open AccessPositive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility
NMDA receptors undergo constant cycling into and out of the postsynaptic density. Here authors show that NMDAR's GluN1 subunit is required to maintain NMDARs at dendritic spine synapses by direct extracellular interaction with the receptor tyrosine kinase EphB2.
- Halley R. Washburn
- , Nan L. Xia
- & Matthew B. Dalva
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Article
| 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 AccessStudying biomolecular folding and binding using temperature-jump mass spectrometry
Native mass spectrometry allows monitoring the folding and interactions of multiple coexisting species but its temporal resolution is traditionally limited. Here, the authors develop a temperature-jump electrospray source for mass spectrometry that enables fast kinetics experiments at different temperatures.
- Adrien Marchand
- , Martin F. Czar
- & Renato Zenobi
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Article
| Open AccessTrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in membrane potential
TrkH is a bacterial ion channel that is regulated by nucleotides and its associated protein TrkA. Here the authors present ADP and ATP bound TrkH-TrkA structures, which reveal the mechanism for the transmission of nucleotide-induced conformational changes in TrkA to the opening of the TrkH channel and further support the proposed gating mechanism with functional studies.
- Hanzhi Zhang
- , Yaping Pan
- & Ming Zhou
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Article
| Open AccessPhysical and behavioral adaptations to prevent overheating of the living wings of butterflies
Butterfly wings have low thermal capacity and thus are vulnerable to damage by overheating. Here, Tsai et al. take an interdisciplinary approach to reveal the organs, nanostructures and behaviors that enable butterflies to sense and regulate their wing temperature.
- Cheng-Chia Tsai
- , Richard A. Childers
- & Nanfang Yu
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| Open AccessHighly durable crack sensor integrated with silicone rubber cantilever for measuring cardiac contractility
Measuring cardiac contractility is challenging. Here, the authors encapsulated a crack-based sensor with polydimethylsiloxane, thereby endowing the sensor with the stability to measure cardiac contractility for up to 26 days as well as monitoring drug-induced cardiac toxicity in cell culture.
- Dong-Su Kim
- , Yong Whan Choi
- & Dong-Weon Lee
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Article
| Open AccessGeometric cues stabilise long-axis polarisation of PAR protein patterns in C. elegans
In the C. elegans zygote, (anterior) aPAR and (posterior) pPAR proteins are key to polarity maintenance, what factors determine the selection of the polarity axis remains unclear. Here authors formulate a reaction-diffusion model in realistic cell geometry and find that long-axis polarisation is promoted by cytosolic dephosphorylation at onset and its steady state determined by minimising the length of the aPAR-pPAR interface.
- Raphaela Geßele
- , Jacob Halatek
- & Erwin Frey
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Article
| Open AccessAn optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells
Adherens junctions (AJs) mediate cell-cell adhesion between epithelial cells but tools to study their dynamic regulation are lacking. Here the authors develop an optochemical tool to stimulate the assembly of AJs through addition of a photocleavable tool and their dissociation upon exposure to light.
- Dirk Ollech
- , Tim Pflästerer
- & Elisabetta Ada Cavalcanti-Adam
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Article
| Open AccessRedox-coupled proton pumping drives carbon concentration in the photosynthetic complex I
Cyanobacteria evolved carbon-concentration mechanisms to enhance the efficiency of photosynthetic CO2 fixation, but the molecular principles have remained unknown. Here authors use cryo-EM to reveal how modular adaptations enabled the photosynthetic complex I from the cyanobacterium Thermosynechococcus elongatus to concentrate CO2.
- Jan M. Schuller
- , Patricia Saura
- & Ville R. I. Kaila
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Article
| Open AccessDisruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis
Acid-sensing ion channel 1a (ASIC1a) mediates acidic neuronal necroptosis via recruiting receptor-interacting protein kinase 1 (RIPK1). Here authors show that auto-inhibition of ASICa prevents RIPK1 recruitment and demonstrate that targeting the auto-inhibition has therapeutic potential to prevent acidotoxicity.
- Jing-Jing Wang
- , Fan Liu
- & Tian-Le Xu
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Article
| Open AccessThe C. difficile toxin B membrane translocation machinery is an evolutionarily conserved protein delivery apparatus
Large Clostridial toxins infiltrate host cells using a translocation domain (LCT-T). Here, using a genomics-driven approach and functional assays, the authors uncover the presence of distant LCT-T homologs in bacteria outside clostridia and provide evidence for a toxic effector function in the gammaproteobacterium Serratia marcescens.
- Kathleen E. Orrell
- , Michael J. Mansfield
- & Roman A. Melnyk
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Article
| Open AccessTranscription reinitiation by recycling RNA polymerase that diffuses on DNA after releasing terminated RNA
Bacterial transcription is terminated when RNA polymerases encounter terminator sequences. Using a single-molecule fluorescence assay, here the authors show that the release of transcript RNA precedes RNA polymerase dissociation and that the remaining RNA polymerase can reinitiate at nearby promoters.
- Wooyoung Kang
- , Kook Sun Ha
- & Changwon Kang
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Article
| Open AccessWASP family proteins regulate the mobility of the B cell receptor during signaling activation
B cell receptors (BCR) capture antigen and initiate downstream antibody responses, but whether and how BCR signaling is regulated by BCR mobility is still unclear. Here the authors show, using single molecule imaging and machine learning analyses, that BCR and CD19 mobility is modulated by the actin nucleation regulators Arp2/3 and N-WASP to control BCR signaling.
- Ivan Rey-Suarez
- , Brittany A. Wheatley
- & Arpita Upadhyaya
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Article
| Open AccessAlternative transcription cycle for bacterial RNA polymerase
In the canonical bacterial transcription, both nascent transcript and polymerase dissociate from template DNA. By employing multi-color single-molecule fluorescence imaging, here the authors show that RNA polymerases remain bound to DNA after the transcript release.
- Timothy T. Harden
- , Karina S. Herlambang
- & Jeff Gelles
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Article
| Open AccessStructural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors
Selectively inhibiting N-Methyl-D-aspartate receptors (NMDARs) containing the GluN2C/2D subunits has been challenging. Here, using electrophysiology and X-ray crystallography, authors show that compounds UBP791 and UBP1700 show over 40- and 50-fold selectivity for GluN2C/2D compared to GluN2A.
- Jue Xiang Wang
- , Mark W. Irvine
- & Hiro Furukawa
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Article
| Open AccessDesign of a unidirectional water valve in Tillandsia
The valve-like trichomes of the desert plant Tillandsia landbeckii allow water acquisition from fog while minimising transpiration. Here, Raux et al. show that a hygroscopic cell-wall adjacent to a semi-permeable plasma membrane at the base of the trichome confers this asymmetry in water conductance.
- Pascal S. Raux
- , Simon Gravelle
- & Jacques Dumais
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Article
| Open AccessThe molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD
The important tuberculosis drug pyrazinamide (PZA) is converted to its active form pyrazinoic acid (POA) in Mycobacterium tuberculosis (Mtb). Here the authors identify the pantothenate biosynthesis pathway enzyme aspartate decarboxylase (PanD) as the target of PZA and determine the POA bound Mtb PanD crystal structure.
- Qingan Sun
- , Xiaojun Li
- & James C. Sacchettini
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Article
| Open AccessGenerating quantitative binding landscapes through fractional binding selections combined with deep sequencing and data normalization
Quantifying the effect of mutations on binding free energy is important to understand protein-protein interaction (PPI). Here the authors develop a method based on yeast display and next-generation sequencing to generate quantitative binding landscapes for any PPI regardless of their Kd value.
- Michael Heyne
- , Niv Papo
- & Julia M. Shifman
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Article
| Open AccessBright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy
Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin.
- Jiwoong Kwon
- , Jong-Seok Park
- & Sang-Hee Shim
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Article
| Open AccessAnnexin-V stabilizes membrane defects by inducing lipid phase transition
Annexins are cytoplasmic proteins, which bind to membranes exposing negatively charged phospholipids in a Ca2+-dependent manner. Here the authors use high-speed atomic force microscopy and other techniques to show that annexin-V self-assembles into highly structured lattices that lead to a membrane phase transition on PS-rich membranes.
- Yi-Chih Lin
- , Christophe Chipot
- & Simon Scheuring
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| Open AccessAssembly and substrate recognition of curli biogenesis system
A major component of bacterial biofilms is curli amyloid fibrils secreted by the curli biogenesis system. Here authors use cryo-EM to visualize the secretion channel complexes (CsgF-CsgG) with and without the curli substrate and provide insights into curli biogenesis.
- Zhaofeng Yan
- , Meng Yin
- & Xueming Li
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Article
| Open AccessResolving kinetic intermediates during the regulated assembly and disassembly of fusion pores
SNAREs mediate the formation of a fusion pore during exocytosis which connects the lumen of a vesicle with the extracellular space. Here, authors use single molecule approaches to define the role of synaptotagmin 1 and NSF in synaptic pore formation and dissolution.
- Debasis Das
- , Huan Bao
- & Edwin R. Chapman
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Article
| Open AccessProgrammed magnetic manipulation of vesicles into spatially coded prototissue architectures arrays
To execute higher-order functions, cells self-assemble into spatially coded tissue configurations. Here the authors magnetically assembly giant unilamellar vesicles into three dimensional tissue-mimic structures with collective osmotic stability.
- Qingchuan Li
- , Shubin Li
- & Xiaojun Han
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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 AccessStructural basis for itraconazole-mediated NPC1 inhibition
Niemann-Pick C1 (NPC1) exports low-density-lipoprotein (LDL)-derived cholesterol from lysosomes and comporses a Sterol-Sensing Domain (SSD). Here authors report a cryo-EM structure of human NPC1 bound to itraconazole which reveals how this binding site in the center of NPC1 blocks a putative lumenal tunnel linked to the SSD.
- Tao Long
- , Xiaofeng Qi
- & Xiaochun Li
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Article
| Open AccessCardiac muscle thin filament structures reveal calcium regulatory mechanism
The contraction of cardiac and skeletal muscles is regulated by Ca2+ released from the sarcoplasmic reticulum in muscle cells. Here the authors provide molecular insights into Ca2+ regulation of muscle contraction by determining the cryo-EM structures of the human cardiac muscle thin filament in the absence and presence of Ca2+.
- Yurika Yamada
- , Keiichi Namba
- & Takashi Fujii
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Article
| Open AccessChromatin fibers stabilize nucleosomes under torsional stress
Torsional stress is generated during DNA replication and transcription, however, the propagation of twist in condensed chromatin is poorly understood. Here the authors measure how force and torque impact chromatin fibers and find that the fibers fold into a left-handed superhelix that can be stabilized by positive torsion, suggesting that chromatin fibers stabilize nucleosomes under torsional stress.
- Artur Kaczmarczyk
- , He Meng
- & Nynke H. Dekker
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Article
| Open AccessImaging of fluorescence anisotropy during photoswitching provides a simple readout for protein self-association
Performing homo-FRET measurements in cells using a fluorescence microscope is challenging, especially when using high numerical aperture objective lenses. Here the authors present a method for improved homo-FRET measurements based on anisotropy changes in photoswitchable fluorescent proteins.
- Namrata Ojha
- , Kristin H. Rainey
- & George H. Patterson
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Article
| Open AccessMicroparticle traction force microscopy reveals subcellular force exertion patterns in immune cell–target interactions
Traction force microscopy is an effective method for measuring cellular forces but it is limited by planar geometry. Here the authors develop a facile method to produce deformable hydrogel particles and a reference-free computational method to resolve surface traction forces from particle shape deformation.
- Daan Vorselen
- , Yifan Wang
- & Julie A. Theriot
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Article
| Open AccessActive topological glass
Glass transition in soft materials can be affected by the topology of constituent particles, but the detail remains elusive. Here, Smrek et al. show that the interplay between circular topology of ring polymers and their active segments generates a new state of matter, namely active topological glass.
- Jan Smrek
- , Iurii Chubak
- & Kurt Kremer
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Article
| Open AccessForces during cellular uptake of viruses and nanoparticles at the ventral side
Many intracellular pathogens mimic extracellular matrix motifs to specifically interact with the host membrane which may influences virus particle uptake. Here authors use single molecule tension sensors to reveal the minimal forces exerted on single virus particles and demonstrate that the uptake forces scale with the adhesion energy.
- Tina Wiegand
- , Marta Fratini
- & Joachim P. Spatz
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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 AccessA mitochondrial megachannel resides in monomeric F1FO ATP synthase
The ATP synthase has been suggested to contain the mitochondrial permeability transition pore (mPTP), which has a crucial role in cell death. Here the authors show that reconstituted ATP synthase monomers form voltage-gated and Ca2+ -activated channels with the key features of mPTP.
- Nelli Mnatsakanyan
- , Marc C. Llaguno
- & Elizabeth A. Jonas
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Article
| Open AccessUltrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings
The ultrastructural details of the periodic scaffold of actin rings under the plasma membrane of axons remain unknown. Here, the authors combine platinum-replica electron and optical super-resolution microscopy and resolve actin rings as braids made of two long, intertwined actin filaments connected by a dense mesh of aligned spectrins.
- Stéphane Vassilopoulos
- , Solène Gibaud
- & Christophe Leterrier
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Article
| Open AccessHelix 8 is the essential structural motif of mechanosensitive GPCRs
GPCRs are versatile cellular sensors for chemical stimuli but the molecular mechanisms underlying mechanically induced GPCR activation have remained elusive. Here authors identify the C-terminal helix 8 (H8) as the essential structural motif endowing H1R and other GPCRs with mechanosensitivity.
- Serap Erdogmus
- , Ursula Storch
- & Michael Mederos y Schnitzler
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Article
| Open AccessA short translational ramp determines the efficiency of protein synthesis
Several factors contribute to the efficiency of protein expression. Here the authors show that the identity of amino acids encoded by codons at position 3–5 significantly impact translation efficiency and protein expression levels.
- Manasvi Verma
- , Junhong Choi
- & Sergej Djuranovic