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Machine learning-based motion tracking reveals an inverse correlation between adhesivity and surface motility of the leptospirosis spirochete
A common approach to study bacterial motility is fluorescent labelling, but this can be hampered by protein expression instability and/or interference with bacterial physiology. Here, Abe et al. describe a machine learning-based method for motion tracking of spirochetes on cultured animal cells, which does not require labelling and might be applied to study motility of other bacterial species.
- Keigo Abe
- , Nobuo Koizumi
- & Shuichi Nakamura
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Transmembrane 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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Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states
The early stages of viral fusogen conformational change required for enveloped viruses to infect cells is unclear. Here, authors capture the herpesvirus fusogen, glycoprotein B, in early transitional states by cryo-EM.
- Momei Zhou
- , Benjamin Vollmer
- & Stefan L. Oliver
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A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers
Protein serial crystallography at X-ray free-electron lasers (XFELs) is a powerful technique for structure determination. Here, authors present a device for sample delivery designed to abate challenges to non-specialists allowing for compound screening.
- Maximilian Wranik
- , Michal W. Kepa
- & Jörg Standfuss
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Cytosolic actin isoforms form networks with different rheological properties that indicate specific biological function
β-actin and γ-actin are nearly identical, and yet incorporate into different cytoskeletal structures. Here, the authors create isoform-pure reconstituted networks and study their structural and mechanical differences, underscoring the significance of the isoforms in diverse cellular functions.
- Peter Nietmann
- , Kevin Kaub
- & Andreas Janshoff
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Assembly mechanism of the inflammasome sensor AIM2 revealed by single molecule analysis
Mechanistic insight into inflammasome formation is important for designing anti-inflammatory interventions. Here, the authors reveal the kinetics and distinct assembly modes of the early stages of the AIM2 inflammasome that detects pathogenic DNA.
- Meenakshi Sharma
- & Eva de Alba
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Article
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Structural basis of a redox-dependent conformational switch that regulates the stress kinase p38α
p38α is a kinase that regulates many cellular processes. Here authors report that redox fluctuations induce conformational changes to fine-tune the p38α activity beyond its activation loop phosphorylation.
- Joan Pous
- , Blazej Baginski
- & Maria J. Macias
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Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8
CCR8 is a promising target in cancer immunotherapy. Here, authors generated mAb1, an antagonist antibody against CCR8 and determined structures of CCR8 in complex with mAb1 or the agonist CCL1, providing insights into CCR8 inhibition and activation.
- Dawei Sun
- , Yonglian Sun
- & Matthieu Masureel
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A 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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Label-free identification of protein aggregates using deep learning
The authors use deep learning to detect and segment unlabeled and unaltered protein aggregates in living cells from transmitted-light images. The method provides a way to quantitatively study protein aggregation dynamics in a simple, fast and accurate way.
- Khalid A. Ibrahim
- , Kristin S. Grußmayer
- & Aleksandra Radenovic
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LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins
Interpretation of lipid-like densities in cryo-EM structures of membrane proteins is challenging. Here authors present LipIDens, enabling molecular dynamics analysis of protein-lipid interactions.
- T. Bertie Ansell
- , Wanling Song
- & Mark S. P. Sansom
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Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration
Synaptotagmin-1 and -7 are calcium sensors that distinctly drive vesicular exocytosis. Here, using wild-type proteins but manipulating the composition of the target membranes, the authors show that synaptotagmin-7 is unusually robust at penetrating membranes.
- Kevin C. Courtney
- , Taraknath Mandal
- & Edwin R. Chapman
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Stochastic chain termination in bacterial pilus assembly
Adhesive type-1 pili from Escherichia coli are filamentous protein complexes consisting of a short tip and a long rod formed by up to several thousand copies of a major subunit. Here, Giese et al. reconstitute the entire type-1 pilus rod assembly reaction in vitro, using all constituent protein subunits, and identify a subunit that acts as an irreversible assembly terminator.
- Christoph Giese
- , Chasper Puorger
- & Rudi Glockshuber
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Dynamical control enables the formation of demixed biomolecular condensates
In this work, the authors report that protein-RNA condensates with shared proteins and distinct RNAs can form and persist in vitro and in cells as distinct entities if the nonshared RNA molecules are dynamically arrested, but the shared protein components are dynamically exchangeable.
- Andrew Z. Lin
- , Kiersten M. Ruff
- & Rohit V. Pappu
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The heat shock protein LarA activates the Lon protease in response to proteotoxic stress
The Lon protease is an important protein degradation machine and is conserved across the three domains of life. Here, the authors describe a small proteotoxic stress-induced protein that functions as an allosteric activator of Lon.
- Deike J. Omnus
- , Matthias J. Fink
- & Kristina Jonas
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Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs
Efficient production of MSC secretome for therapeutic applications remains a challenging task. Here, the authors present an approach whereby an acoustofluidic mechanobiological environment can form reproducible 3D MSC aggregates, allowing for secretome production with high efficiency.
- Ye He
- , Shujie Yang
- & Tony Jun Huang
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Quantification 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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Myr-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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HIV-1 Gag targeting to the plasma membrane reorganizes sphingomyelin-rich and cholesterol-rich lipid domains
Quantitative microscopies and specific lipid probes revealed that multimerizing HIV-1 Gag in the plasma membrane inner leaflet brings the outer leaflet sphingomyelin-rich and cholesterol-rich lipid domains closer in a curvature-dependent manner.
- Nario Tomishige
- , Maaz Bin Nasim
- & Toshihide Kobayashi
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Vesicles driven by dynein and kinesin exhibit directional reversals without regulators
Intracellular transport along microtubules involves runs, pauses and directional reversals. Here, D’Souza et al. mimic these dynamics in vitro using a minimal system of Dynein-Dynactin-BICD2 and Kinesin-3 on vesicles without the need for regulators.
- Ashwin I. D’Souza
- , Rahul Grover
- & Stefan Diez
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Activation and substrate specificity of the human P4-ATPase ATP8B1
Asymmetric phospholipid distribution in cell membranes is vital for cellular function. Here, authors reveal how ATP8B1, a P4-ATPase, can transport different lipids, including phosphatidylinositol.
- Thibaud Dieudonné
- , Felix Kümmerer
- & Poul Nissen
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Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT
Sodium glucose transporters are critical for maintaining glucose homeostasis. Here, authors provide a detailed framework for how SGLTs utilize cellular membrane potentials to stabilize their substrate accepting conformation leading to accelerated transport.
- Farha Khan
- , Matthias Elgeti
- & Jeff Abramson
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Mechanically-primed voltage-gated proton channels from angiosperm plants
The authors describe a proton channel protein in the vasculature of Arabidopsis thaliana that requires both mechanical and electrical stimuli to turn on. A mechanistic analysis identifies the molecular determinants for the hybrid activation process.
- Chang Zhao
- , Parker D. Webster
- & Francesco Tombola
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Patterning 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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Simulation-guided engineering of split GFPs with efficient β-strand photodissociation
Green fluorescent proteins (GFPs) are ubiquitous for protein tagging and live cell imaging. Here, authors have used computational methods to engineer a fast-dissociating split GFP, which could be used to study macromolecular interactions.
- Yasmin Shamsudin
- , Alice R. Walker
- & Steven G. Boxer
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The structural and functional investigation into an unusual nitrile synthase
The nitrile synthase AetD is a crucial component in the biosynthetic pathway of neurotoxin aetokthonotoxin (AETX). Here, the authors solved crystal structures of AetD in complex with different substrates, revealing that AetD represents a new type of HO-like diiron enzyme and the possibility of expanding its substrate spectrum.
- Hao Li
- , Jian-Wen Huang
- & Chun-Chi Chen
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Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
T-box riboswitches are RNA-based gene regulators, composed of highly structured noncoding RNAs: the T-box and a tRNA ligand. Here, the authors assess the folding of a translational T-box aptamer and dissect the role of Mg2+, intra- and intermolecular RNA-RNA interactions in modulating its folding and function.
- Xiaolin Niu
- , Zhonghe Xu
- & Xianyang Fang
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The GET insertase exhibits conformational plasticity and induces membrane thinning
Tail-anchored (TA) membrane protein biogenesis is mediated by the GET insertase. Here, authors present cryo-EM and X-ray structures, MD simulations and functional data for human and fungal insertases showing membrane remodeling for TA insertion.
- Melanie A. McDowell
- , Michael Heimes
- & Irmgard Sinning
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Multiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes
Fast discrimination of SARS-CoV-2 variants in clinical samples remains a challenge. Here, authors report on single molecule nanopore sensing combined with DNA molecular probes to simultaneously detect various antigens and RNA mutations of SARS-CoV-2 variants in patient samples.
- Ren Ren
- , Shenglin Cai
- & Joshua B. Edel
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Cryo-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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Long-term cargo tracking reveals intricate trafficking through active cytoskeletal networks in the crowded cellular environment
Leveraging a label-free interferometric scattering microscope, scientists tracked numerous cargos within a crowded cellular environment. Intriguingly, cells employ effective strategies echoing human transportation systems to manage such transportation hurdles.
- Jin-Sung Park
- , Il-Buem Lee
- & Minhaeng Cho
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Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation
Using single-molecule FRET, the authors discover hidden structural subpopulations of the intrinsically disordered prion-like low-complexity domain of FUS and dissect key molecular events that drive dynamic network formation during phase separation.
- Ashish Joshi
- , Anuja Walimbe
- & Samrat Mukhopadhyay
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Local membrane source gathering by p62 body drives autophagosome formation
Phase separated p62 body plays pivotal roles in autophagy. Here, the authors describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation.
- Xuezhao Feng
- , Daxiao Sun
- & Na Mi
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Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding
FBF-2 and LST-1 repress gld-1 mRNA expression to maintain C. elegans germline stem cells. The authors show that an intrinsically-disordered region of FBF-2 autoinhibits its RNA binding. LST-1 antagonizes this interaction to promote RNA binding.
- Chen Qiu
- , Zihan Zhang
- & Traci M. Tanaka Hall
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Environmental memory boosts group formation of clueless individuals
Indirect coordination among individuals through the environment typically requires some basic levels of communication and information processing. Dias et al. introduce a coordination mechanism that emerges in a population of clueless individuals, facilitated by environmental memory, culminating in group formation.
- Cristóvão S. Dias
- , Manish Trivedi
- & Giorgio Volpe
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Cryo-EM structure of TMEM63C suggests it functions as a monomer
TMEM63s are mechanosensitive ion channels activated by hypo-osmolality. Here, the authors determine the cryo-EM structure of mouse TMEM63C confirming its predominant monomeric state and the significance of TM0-TM6 coupling in channel activity.
- Yuqi Qin
- , Daqi Yu
- & Shangyu Dang
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Nde1 promotes Lis1-mediated activation of dynein
Lis1 and Nde1/Ndel1 mediate the initiation of dynein-driven transport, but the mechanism remains unclear. Here, the authors reveal that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of active dynein transport machinery.
- Yuanchang Zhao
- , Sena Oten
- & Ahmet Yildiz
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Progesterone activation of β1-containing BK channels involves two binding sites
Progesterone is used in recovery of cerebral ischemia however the mechanism of action is unknown. Authors report here that micromolar progesterone activates mouse cerebrovascular myocyte BK channels, involving two steroid binding sites.
- Kelsey C. North
- , Andrew A. Shaw
- & Alex M. Dopico
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Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter
Multidrug resistance through active extrusion of molecules by transporters is a pressing clinical problem. Here, authors dissect the mechanism by which an ABC transporter from B. Subtilis binds and removes drugs by consuming the energy of ATP hydrolysis.
- Qingyu Tang
- , Matt Sinclair
- & Hassane S. Mchaourab
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Cryo-EM structures of human magnesium channel MRS2 reveal gating and regulatory mechanisms
Magnesium homeostasis is key for cellular functions. Here, authors report structures of human mitochondrial Mg2+ channel MRS2 and identified key residues in gating. This work provides insights into the gating and regulatory mechanisms of MRS2.
- Louis Tung Faat Lai
- , Jayashree Balaraman
- & Doreen Matthies
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Targeting nucleic acid phase transitions as a mechanism of action for antimicrobial peptides
In this work the authors describe antimicrobial peptides (AMPs)-driven phase transitions of intracellular nucleic acids, whereby AMPs induce compaction and phase separation of nucleic acids, resulting in their sequestration and eventual cell death.
- Tomas Sneideris
- , Nadia A. Erkamp
- & Tuomas P. J. Knowles
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Structural basis of peptide secretion for Quorum sensing by ComA
Quorum sensing is a regulatory mechanism controlling bacterial signaling and ComA, a conserved efflux pump, is responsible for the maturation and secretion of peptide signals. Here, authors determine the 3D structure and demonstrate its function as an ABC transporter.
- Lin Yu
- , Xin Xu
- & Min Luo
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Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans
In this work, the authors combine cryo-electron tomography of vitrified virions, mass spectrometry, modeling, molecular dynamics and infectivity assay and report that a hinge glycan on viral spike protein influences virus infection and immune evasion.
- David Chmielewski
- , Eric A. Wilson
- & Wah Chiu
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Elevator-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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Dual function of OmpM as outer membrane tether and nutrient uptake channel in diderm Firmicutes
Outer membrane tethering is important for cell envelope integrity in diderm bacteria. Here, the authors present structures and functional analyses of the stalked porin OmpM, which is the main outer membrane tethering system within the Terrabacteria.
- Augustinas Silale
- , Yiling Zhu
- & Bert van den Berg
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Structure and function of the EA1 surface layer of Bacillus anthracis
S-layers form continuous protein lattices on the surface of bacteria. Here, authors use S-layer depolymerizing nanobodies to solve the structure of the EA1 S-layer in the pathogen Bacillus anthracis and show its role as cell wall supportive structure”
- Adrià Sogues
- , Antonella Fioravanti
- & Han Remaut
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DNA strand breaks and gaps target retroviral intasome binding and integration
Here the authors use biochemical assays and single molecule imaging to show that DNA breaks and single-stranded gaps modulate dynamic PFV retroviral intasome interactions with target DNA and encourage site-specific integration.
- Gayan Senavirathne
- , James London
- & Kristine E. Yoder
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Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus
Studying rare species in mixtures is challenging. Here, authors utilize on-and-off optical plasmonic trapping to control SERS-active nanocavity to analyse pH-dependent amylin species at single-molecule level, unveiling amyloid aggregation mechanisms.
- Wenhao Fu
- , Huanyu Chi
- & Jinqing Huang
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In situ quantification of osmotic pressure within living embryonic tissues
Osmotic pressure is thought to play a key role in many cellular and developmental processes, but remains challenging to measure it in cells and tissues. Here, the authors present a sensor based on double emulsion droplets that allows quantification of osmotic pressure in situ and in vivo.
- Antoine Vian
- , Marie Pochitaloff
- & Otger Campàs
Environmental modulation of global epistasis in a drug resistance fitness landscape