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| Open AccessHydrophobic mismatch drives self-organization of designer proteins into synthetic membranes
The organization of membrane proteins is critical to cellular function. Here the authors explore how computational protein design, MD simulation, and cell-free systems can be combined to elucidate how membrane-protein hydrophobic mismatch affects protein folding and organization in synthetic lipid membranes.
- Justin A. Peruzzi
- , Jan Steinkühler
- & Neha P. Kamat
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Article
| Open AccessTension activation of mechanosensitive two-pore domain K+ channels TRAAK, TREK-1, and TREK-2
TRAAK, TREK-1 and TREK-2 are mechanosensitive potassium channels involved in action potential propagation among other roles. Here, authors quantify their tension response and show ultrasound can generate tension to activate ion channels.
- Ben Sorum
- , Trevor Docter
- & Stephen G. Brohawn
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| Open AccessAdhesion energy controls lipid binding-mediated endocytosis
Many bacterial toxins and viruses deform membranes prior to entering cells via clathrin independent endocytosis. Here the authors show that multivalent lipid binding by globular particles can exceed a threshold adhesion energy required for membrane deformation and that this is sufficient for internalization.
- Raluca Groza
- , Kita Valerie Schmidt
- & Helge Ewers
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Article
| Open AccessStructural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1
Yeast cadmium factor 1 (Ycf1), a heavy metal and glutathione transporter, is regulated by an intrinsically disordered region called the regulatory domain. In this work, the authors show that this domain controls activity through autoinhibition of the glutathione cavity when it is dephosphorylated.
- Nitesh Kumar Khandelwal
- & Thomas M. Tomasiak
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Article
| Open AccessDual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin
The poison dart toxin batrachotoxin is the most lethal voltage-gated sodium channel toxin. Here authors identify the toxin bound specifically at two homologous receptor sites, which cause channel hyperactivation by positively modulating channel gating and altering ion conductance.
- Lige Tonggu
- , Goragot Wisedchaisri
- & William A. Catterall
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| Open AccessFunctional regulation of aquaporin dynamics by lipid bilayer composition
Membrane proteins depend on their lipid environments. Using aquaporin as a model, the authors show that the choice of lipid bilayer fundamentally affects membrane protein structure, thermodynamics, kinetic, and function, even to the point of lipid-based inhibition.
- Anh T. P. Nguyen
- , Austin T. Weigle
- & Diwakar Shukla
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| Open AccessMeasuring sub-nanometer undulations at microsecond temporal resolution with metal- and graphene-induced energy transfer spectroscopy
Studying the fluctuations of biological membranes with high resolution is challenging. Here, the authors combine metal- and graphene-induced energy transfer (MIET/GIET) with fluorescence correlation spectroscopy (FCS) to monitor such fluctuations with nanometer and microsecond resolution.
- Tao Chen
- , Narain Karedla
- & Jörg Enderlein
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Article
| Open AccessDirect observation of autoubiquitination for an integral membrane ubiquitin ligase in ERAD
The stoichiometry of Hrd1, an integral membrane E3 ubiquitin ligase is critical to maintaining proteostasis in the endoplasmic reticulum. Here, the authors establish a single-molecule counting approach coupled with a single-molecule in vitro ubiquitination system to determine the functional stoichiometry of Hrd1.
- Basila Moochickal Assainar
- , Kaushik Ragunathan
- & Ryan D. Baldridge
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Article
| Open AccessPhotolipid excitation triggers depolarizing optocapacitive currents and action potentials
Inspired by thermal optocapacitive approaches at regulating neuronal activity, the authors explore a photolipid-based non-thermal optocapacitive method that allows for regulating voltage-gated and mechanosensitive ion channels using light.
- Carlos A. Z. Bassetto Jr
- , Juergen Pfeffermann
- & Peter Pohl
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Article
| Open AccessOverlay databank unlocks data-driven analyses of biomolecules for all
In this work, the authors report NMR lipids Databank to promote decentralised sharing of biomolecular molecular dynamics (MD) simulation data with an overlay design. Programmatic access enables analyses of rare phenomena and advances the training of machine learning models.
- Anne M. Kiirikki
- , Hanne S. Antila
- & O. H. Samuli Ollila
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Article
| Open AccessNonuniversal impact of cholesterol on membranes mobility, curvature sensing and elasticity
Cholesterol both thickens and condenses membranes, yet it also softens them under certain conditions. Here, authors uncover cholesterol’s dual role in the delicate balance of rigidity and flexibility in membranes, crucial for diverse biological functions.
- Matthias Pöhnl
- , Marius F. W. Trollmann
- & Rainer A. Böckmann
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Article
| Open AccessTransmembrane coupling of liquid-like protein condensates
Using a freestanding planar lipid membrane system, the authors show that liquid-like protein condensates on one side of a lipid membrane colocalize with those on the opposite side, suggesting a mechanism of information transfer across biological membranes.
- Yohan Lee
- , Sujin Park
- & Jeanne C. Stachowiak
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Article
| Open AccessA dynamic partitioning mechanism polarizes membrane protein distribution
Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.
- Tatsat Banerjee
- , Satomi Matsuoka
- & Pablo A. Iglesias
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Article
| Open AccessQuantification of ligand and mutation-induced bias in EGFR phosphorylation in direct response to ligand binding
The authors show that the oncogenic L834R EGFR mutation induces bias in EGFR signal transduction across the plasma membrane. While EGFR signalling is biased toward Y1068 phosphorylation, the mutation switches the preference to Y1173 phosphorylation.
- Daniel Wirth
- , Ece Özdemir
- & Kalina Hristova
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| Open AccessMyr-Arf1 conformational flexibility at the membrane surface sheds light on the interactions with ArfGAP ASAP1
An integrated approach combing solution and solid-state NMR, molecular dynamics simulations and neutron reflectometry is applied to characterize dynamic membrane bound forms of ADP-ribosylation factor 1 (Arf1).
- Yue Zhang
- , Olivier Soubias
- & R. Andrew Byrd
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Article
| Open AccessPatterning and dynamics of membrane adhesion under hydraulic stress
Hydraulic fracturing remodels cell-cell adhesions in physiology and during development. Here, authors combine vesicle experiments and computational modeling to identify the physical principles behind biological fracking.
- Céline Dinet
- , Alejandro Torres-Sánchez
- & Margarita Staykova
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Article
| Open AccessCryo-EM structures of the plant anion channel SLAC1 from Arabidopsis thaliana suggest a combined activation model
Phosphorylation-mediated activation of SLAC1 anion channel is crucial in plant responses for abiotic stresses including drought. Here, authors determine the open and closed structures of SLAC1, revealing how phosphorylation can activate SLAC1.
- Yeongmok Lee
- , Hyeon Seong Jeong
- & Sangho Lee
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Article
| Open AccessElevator-like movements of prestin mediate outer hair cell electromotility
Probing the molecular dynamics of the membrane motor, prestin, with biophysical measures and MD simulations, Kuwabara et al. find that an elevator-like domain movement across the membrane produces the unique piezoelectric behavior.
- Makoto F. Kuwabara
- , Bassam G. Haddad
- & Dominik Oliver
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Article
| Open AccessStructural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels that produce Ca2+ oscillations in response to GPCR and RTK activation. Here, Paknejad et al. resolve the conformational landscape of IP3Rs that gives rise to the biphasic dependence on Ca2+ for channel activity.
- Navid Paknejad
- , Vinay Sapuru
- & Richard K. Hite
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Article
| Open AccessLigand activation mechanisms of human KCNQ2 channel
The potassium channel KCNQ2 can be activated by analgesics and antiepileptic drugs via an unclear mechanism. Here authors report structures of KCNQ2-CaM in complex with cannabidiol, PIP2, and HN37 and elucidate the mechanisms of activation.
- Demin Ma
- , Yueming Zheng
- & Jiangtao Guo
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Article
| Open AccessStructural basis of promiscuous substrate transport by Organic Cation Transporter 1
OCT1 plays an important role in the uptake of drugs and metabolites in the liver. Here, authors present the structure of OCT1 to understand how it recognizes and transports a wide range of drugs and substrates.
- Yi C. Zeng
- , Meghna Sobti
- & Alastair G. Stewart
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Article
| Open AccessOpen structure and gating of the Arabidopsis mechanosensitive ion channel MSL10
The Arabidopsis mechanosensitive channel MSL10 plays a crucial role in hypo-osmotic shock adaptation and programmed cell death induction. Here, the authors reveal the structural mechanism underlying MSL10 channel gating.
- Jingying Zhang
- , Grigory Maksaev
- & Peng Yuan
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Article
| Open AccessStructural mechanisms of the human cardiac sodium-calcium exchanger NCX1
Here authors present the cryo-EM structures of human cardiac NCX1, elucidating key structural elements for ion exchange and modulation by cytosolic Ca2+ and Na+.
- Jing Xue
- , Weizhong Zeng
- & Youxing Jiang
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Article
| Open AccessBiomolecular condensates modulate membrane lipid packing and hydration
Nano-environmental probes and advance imaging microscopy provide deep insight into protein phase separation and the interaction of condensates with membranes, revealing that wetting by condensates can modulate membrane lipid packing and hydration.
- Agustín Mangiarotti
- , Macarena Siri
- & Rumiana Dimova
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Article
| Open AccessSensing their plasma membrane curvature allows migrating cells to circumvent obstacles
Motile cells must navigate complex environments. Here the authors use state-of-the-art imaging, coarse-grained MD simulations and experimental biophysics to show that cells sense their plasma membrane curvature to circumvent obstacles.
- Ewa Sitarska
- , Silvia Dias Almeida
- & Alba Diz-Muñoz
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| Open AccessExperimental and theoretical model for the origin of coiling of cellular protrusions around fibers
The leading edges of cellular protrusions coil around extracellular fibers and other fibrous structures such as axons. Combining 3D imaging with theoretical models, the authors show that coiling occurs naturally on curved surfaces due to energy minimization.
- Raj Kumar Sadhu
- , Christian Hernandez-Padilla
- & Nir S. Gov
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Article
| Open AccessStructural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain
G protein-coupled receptors (GPCRs) are involved in many physiological processes and are targets of intense drug discovery research. Here, the authors describe llama-derived nanobodies that allosterically modulate rhodopsin, a prototypical GPCR.
- Arum Wu
- , David Salom
- & Krzysztof Palczewski
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Article
| Open AccessMolecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids
CLC transporters are regulated by nucleotides and phospholipids. Here cryo-EM structure of Arabidopsis CLCa in complex with ATP and PIP2 and electrophysiological analysis suggests the underlying regulatory mechanisms of both nucleotides and phospholipids.
- Zhao Yang
- , Xue Zhang
- & Peng Zhang
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Article
| Open AccessMembrane mediated mechanical stimuli produces distinct active-like states in the AT1 receptor
The AT1 GPCR plays an essential role in cardiovascular regulation and may be activated by the peptide AngII as well as membrane stretch. Here, Poudel et al. use molecular simulations to show that membrane-mediated activation produces distinct active-like conformations when compared to activation by AngII.
- Bharat Poudel
- , Rajitha Rajeshwar T
- & Juan M. Vanegas
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| Open AccessArchitecture and autoinhibitory mechanism of the plasma membrane Na+/H+ antiporter SOS1 in Arabidopsis
SOS1 is a unique electroneutral Na+ /H+ antiporter at the plasma membrane of higher plants and plays a central role in resisting salt stress. Here, the authors report the structures of SOS1 in occluded state, identify the key autoinhibitory elements, and elucidate their molecular mechanism.
- Yuhang Wang
- , Chengcai Pan
- & Yan Zhao
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Article
| Open AccessCysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR)
Oxidation of ryanodine receptor calcium channels play a critical role in the onset of many cardiac diseases. Here, authors identify specific amino acids that cause ryanodine receptor malfunction during oxidative stress.
- Roman Nikolaienko
- , Elisa Bovo
- & Aleksey V. Zima
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Article
| Open AccessThe structural basis of divalent cation block in a tetrameric prokaryotic sodium channel
Divalent cation block is observed in various tetrameric ion channels. Here, authors use X-ray crystallography, electrophysiology and molecular dynamics simulations to reveal the mechanism of the divalent cation block on a prokaryotic sodium channel.
- Katsumasa Irie
- , Yoshinori Oda
- & Yoshinori Fujiyoshi
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Article
| Open AccessA mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity
Mechanosensitive channels exhibit large structural variations. Here, the authors reveal that OSCA channels exhibit different oligomeric states and are gated/regulated by lipids at different locations in response to physical forces.
- Mingfeng Zhang
- , Yuanyue Shan
- & Duanqing Pei
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Article
| Open AccessRapid and reversible optical switching of cell membrane area by an amphiphilic azobenzene
The surface area of living cells is tightly regulated. Here, authors show that the surface area and shape of cells can be reversibly manipulated with light using amphiphilic molecular photoswitches that enter and leave the membrane.
- Fabian Höglsperger
- , Bart E. Vos
- & Bart Jan Ravoo
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Article
| Open AccessStructural insights into perilipin 3 membrane association in response to diacylglycerol accumulation
Perilipin 3 binds to emerging lipid droplets from the endoplasmic reticulum. Choi and Ajjaji et al characterize the molecular mechanisms of Perilipin 3 recruitment to membranes and uncover a function for the PAT domain in diacylglycerol sensing.
- Yong Mi Choi
- , Dalila Ajjaji
- & Michael V. Airola
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Article
| Open AccessAsymmetric pendrin homodimer reveals its molecular mechanism as anion exchanger
Pendrin SLC26A4 plays an important role for anion balance. Here, authors resolve cryo-EM structures of pendrin performing co-incident uptake and secretion of anions, providing a structural basis of this anion exchange mechanism.
- Qianying Liu
- , Xiang Zhang
- & Zhenguo Chen
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Article
| Open AccessWetting and complex remodeling of membranes by biomolecular condensates
In this work, the authors investigated on the interaction of biomolecular condensates with membranes and report that they can exhibit two wetting transitions modulated by membrane or milieu composition. Condensate adhesion can trigger intriguing ruffling of the membrane interface into complex finger-like structures.
- Agustín Mangiarotti
- , Nannan Chen
- & Rumiana Dimova
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Article
| Open AccessAntibody binding reports spatial heterogeneities in cell membrane organization
The organization of proteins and sugars on the cell membrane is crucial for cell signaling and function. Here, authors develop molecular probes and simulations to characterize the spatial organization of macromoleucles on live cell membranes.
- Daniel P. Arnold
- , Yaxin Xu
- & Sho C. Takatori
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Article
| Open AccessStructural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex
Whether anionic phospholipids required for respiratory supercomplex (SC) formation is unclear. Here authors resolve SCs from a wild type and cardiolipin-deficient yeast strain at 3.2- 3.3 Å resolution to show that cardiolipin can be replaced by phosphatidylglycerol.
- Corey F. Hryc
- , Venkata K. P. S. Mallampalli
- & William Dowhan
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Article
| Open AccessStructural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein
The authors report the structure of human oncochannel TRPV6 in complex with the plant derived phytoestrogen genistein. The structure provides insights into genistein binding in the channel pore, and how it acts as blocker and gating modifier, suggesting a mechanism of inhibition that can be explored for the structure-based drug design.
- Arthur Neuberger
- , Yury A. Trofimov
- & Alexander I. Sobolevsky
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Article
| Open AccessStructural and functional analysis of human pannexin 2 channel
The PANX2 channel is involved in skin homeostasis and neuronal development, but the molecular basis of channel function remains largely unknown. Here, the authors provide detailed analysis of the structure, function, and pharmacology of human PANX2.
- Zhihui He
- , Yonghui Zhao
- & Peng Yuan
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Article
| Open AccessTransmembrane signaling by a synthetic receptor in artificial cells
Transmembrane signaling is the core adaptation in nature that allows cells to communicate. Here, the authors engineer signaling through the lipid bilayer using chemical, synthetic receptors for their use in the design of artificial cells.
- Ane Bretschneider Søgaard
- , Andreas Bøtker Pedersen
- & Alexander N. Zelikin
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Article
| Open AccessInsights into membrane association of the SMP domain of extended synaptotagmin
The SMP domain of E-Syts is a newly identified lipid transfer module with unclear mechanisms. Here, authors show that it uses its tip region to associate with the extremely curved or negatively charged membranes to extract and unload lipids.
- Yunyun Wang
- , Zhenni Li
- & Xin Bian
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Article
| Open AccessPhotocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1
The Ca2+ ion channel Orai1 is crucial in immune cells. Here, the authors applied genetic code expansion to transfer light-sensitivity to the Orai1 channel and achieved precise control over its function.
- Lena Maltan
- , Sarah Weiß
- & Isabella Derler
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Article
| Open AccessPeriodic temperature changes drive the proliferation of self-replicating RNAs in vesicle populations
How primordial cells could achieve inheritance of encapsulated components is still an open question. Here, the authors show that ribozymes can assemble in active forms and replicate in populations of membrane vesicles thanks to freeze-thaw cycles.
- Elia Salibi
- , Benedikt Peter
- & Hannes Mutschler
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Article
| Open AccessStructure and mechanism of a tripartite ATP-independent periplasmic TRAP transporter
Bacteria and archaea use tripartite ATP-independent periplasmic (TRAP) transporters to import essential nutrients. Davies et al. report a high resolution structure of a TRAP and show that it uses an ‘elevator-with-an operator’ mechanism.
- James S. Davies
- , Michael J. Currie
- & Renwick C. J. Dobson
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Article
| Open AccessMembrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1
Tandem pore (K2P) potassium channels set the cellular resting membrane potential in tissues throughout the body. Here, authors show how the composition of phospholipid within the bilayer may directly alter gating in this family of ion channels.
- Philipp A. M. Schmidpeter
- , John T. Petroff II
- & Paul M. Riegelhaupt
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Article
| Open AccessA bivalent remipede toxin promotes calcium release via ryanodine receptor activation
Insect toxins with tandem repeats of neurotoxin domains have been found with enhanced receptor avidity. Here, the authors describe a bivalent toxin from remipede venom that targets ryanodine receptors, a rare target for animal venoms.
- Michael J. Maxwell
- , Chris Thekkedam
- & Mehdi Mobli
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Article
| Open AccessTetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes
Migrasomes are signaling organelles that form in retraction fibers of migrating cells. Here authors show that migrasomes form by a two-stage process: an initial local membrane swelling matures and is stabilized by recruited tetraspanin proteins.
- Raviv Dharan
- , Yuwei Huang
- & Raya Sorkin