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Myeloperoxidase, a highly expressed neutrophil protein, disassembles nucleosomes, facilitating neutrophil extracellular trap (NET) formation, and binds stably to NETs extracellularly.

High-resolution structures of the Photorhabdus luminescens TcA toxin subunit and the entire Tc toxin complex reveal important new insights into Tc complex structure and function.

Specificity in interactions with otherwise common glycan structures is likely achieved through glycan context. Here, the authors show that such glycan context is generated through tunable glycan arrangements that are translated into function by galectins.

The TcA component of Photorhabdus luminescens ABC-type toxin complexes forms a transmembrane pore and injects TcC, the functional component of the toxin, into the target cell by means of a syringe-like mechanism.

Structural insights into ultrafast Ca²⁺ transport by plasma membrane Ca²⁺-ATPases are provided, highlighting an essential role for PtdIns(4,5)P₂ dynamics.

The first high-resolution structure of a human actomyosin complex reveals the interface between F-actin and myosin in near-atomic detail.

Electron cryomicroscopy reveals the three-dimensional structure of F-actin at a resolution of 3.7 Å in complex with tropomyosin at a resolution of 6.5 Å; the stabilizing interactions and the effects of disease-causing mutants are also investigated.

Entomopathogenic bacteria used for pest control secrete potent Tc toxins. Here, the authors combine biochemistry, solution and solid-state NMR spectroscopy and cryo-EM to show in atomic detail how the toxin disrupts the host cell cytoskeleton and kills the target cell.

The pointed end of actin filaments is a dominant site of actin depolymerization. Here, the authors show how the actin modulators phalloidin and DNase I interact with the pointed end to either stabilize its arrangement or to promote its disassembly.

The bacterial toxin Makes caterpillars floppy 1 promotes apoptosis in insects. Combining single-particle cryo-EM and biochemistry, the authors determined the molecular architecture of the toxin and revealed its autoproteolytic activation mechanism.

The assembly of branched actin networks depends on the heterodimeric capping protein CP/CapZ. Combining cryoEM, in vitro reconstitution and cell biological assays, the authors show that CP not only prevents actin filament elongation but also selectively masks actin filament ends to promote nucleation.

Release of inorganic phosphate (P_i) from actin marks older actin filaments for disassembly. Here, the authors show how P_i exits the F-actin interior through a ‘molecular backdoor’. The backdoor arrangement is distorted in a disease-linked actin variant.

Cryo-electron microscopy structures of skeletal F-actin show solvent-driven rearrangements governing actin filament assembly and aging with potential application in design of drugs and small molecules for imaging and therapy.

A genome-wide CRISPR–Cas9-mediated knockout screen in Drosophila cells identifies Visgun as a proteinaceous receptor for toxin complex toxins, demonstrating the utility of this approach for investigating insecticidal toxins and pathogens.

A specialized subpopulation of Yersinia entomophaga cells uses a RoeA-regulated, temperature- and pH-dependent type 10 secretion system to mediate lytic Tc toxin release.

A cryo-electron tomography study reports the structure of thick myosin filaments of mouse cardiac muscle in the relaxed state in situ and the MyBP-C links that connect them with the surrounding thin actin filaments.

Slowpoke (Slo) channels are voltage-gated potassium channels that are activated by high intracellular Ca²+ concentrations, and they are targets for insecticides and antiparasitic drugs. Here, the authors present the cryo-EM structures of the Drosophila melanogaster Slo channel in the Ca²+-bound and Ca²+-free conformations, as well as in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside and discuss the mechanisms by which they affect the activity of Slo.

The nucleotidyl cyclase toxin exoenzyme Y (ExoY), which is secreted by the human pathogens Pseudomonas aeruginosa and Vibrio vulnificus is activated by actin. Here, the authors present the cryo-EM structures of PaExoY bound to F-actin and VvExoY in complex with G-actin-profilin. These structures together with molecular dynamics simulations and enzymatic assays provide insights into the activation mechanism for both bacterial cyclase toxin families that interact with either F- or G-actin.

Although Tc toxins are a major class of bacterial toxin translocation systems, little is known about their receptor binding. Here, the authors identify heparins/heparan sulfates and Lewis antigens as receptors for different Tc toxins, determine cryo-EM structures of three toxin-glycan complexes and propose a two-step cell adhesion mechanism for Tc toxins.

Tc toxins are a major class of bacterial toxin translocation systems that inject toxic enzymes into target cells. Here the authors present functional and structural data showing that the toxic enzyme can be replaced by other small proteins and identify prerequisites required for successful translocation, which could facilitate the development of functional Tc-based protein injection devices.

TomoTwin is a deep metric learning-based particle picking method for cryo-electron tomograms. TomoTwin obviates the need for annotating training data and retraining a picking model for each protein.

Using electron cryomicroscopy, the structure of the rabbit RyR1 calcium channel is determined at 6.1 Å resolution in the closed state and 8.5 Å in the open state, revealing how calcium binding to the EF-hand of RyR1 regulates channel opening and facilitates calcium-induced calcium release.

Cryo-EM structures of F-actin captured in different nucleotide states, by using nucleotide analogs or small molecules, reveal different conformational states linked to ATP hydrolysis.

A high-resolution cryo-electron microscopy structure of a complete Tc holotoxin complex reveals the precise mechanism of Tc toxin assembly, gate opening and release of the cytotoxic enzyme into the translocation channel.

The architecture of the Listeria monocytogenes ClpXP machine is revealed by cryo-EM analyses explaining how the symmetry mismatch between hexameric ClpX and heptameric ClpP rings is resolved for functional coordination.

High-throughput single particle cryo-EM, for instance in drug research, requires the automation of the single particle analysis workflow. Here, the authors present TranSPHIRE, a software package that allows the fully-automated, feedback-driven processing of cryo-EM datasets during data acquisition.

Automated single-particle picking in electron cryo-microscopy data has seen important advances in the past couple of years and now enables computer-assisted particle selection even for challenging datasets. These advances have implications for streamlined and automated image processing, with potential benefits for improving the resolution of resulting structures.

A combination of cryo-EM structures and experiments using liposomes and lipid nanodiscs elucidates how the Tse6 effector is loaded into the type VI secretion system and travels across membranes to intoxicate target cells.

A cryo-EM structure of toxin component TcdA1 embedded in lipid nanodiscs reveals details of the mechanism used by this bacterial toxin to insert into the host cell membrane.

The Review provides an overview of ion-channel insecticide targets, with a focus on their mechanisms of action, and offers a perspective for structure-based development of insecticides.

Most compounds form crystals so small that scientists cannot experimentally determine their atomic structures using X-ray crystallography. Microcrystal electron diffraction now provides a unique solution for this challenge.

During cell division, kinetochores anchor chromosomes to spindle microtubules. Here, the authors report a comprehensive structure–function analysis of the kinetochore’s main microtubule receptor, the KMN network, shedding new light on its organization.

Structures of separase in complex with either securin or cyclin B–CDK1 shed light on the regulation of chromosome separation during the cell cycle.

The CCR4-NOT complex shortens poly(A) tails of messenger RNAs. By biochemical reconstitution of the entire human CCR4-NOT complex, the authors show the stimulatory roles of non-enzymatic subunits and the importance of the interaction between CAF40 and RNA binding proteins in targeted deadenylation.

The Mon1-Ccz1 (MC1) complex is a Rab guanine nucleotide exchange factor (RabGEF) for Ypt7/Rab7 important for endosomal maturation. Here the authors present the biochemical and structural characterization of MC1, elucidating its catalytic mechanism and showing that MC1 represents novel class of RabGEFs.

The venom of Latrodectus spiders contains seven Latrotoxins (LaTXs), among them α-latrocrustatoxin (LCT) and δ- latroinsectotoxins δ-LIT. LaTXs bind to specific receptors on the surface of neuronal cells and target the molecular exocytosis machinery. Here, the authors present the cryo-EM structure of the α-LCT monomer and the δ-LIT dimer, which reveal that LaTXs are organized in four domains and they discuss the potential oligomerisation mechanism that takes place before LaTXs membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca²⁺ ions.

Wagner and Raunser recently presented a deep learning based particle picking program for Cryo-EM, crYOLO. Here they discuss recent improvements to the program, a graphical user interface and share their thoughts on desired future developments.

The crystal structure of the complex formed by the death domains from Fas and FADD at physiological pH is now solved, revealing a 5:5 complex that is supported by electron microscopy data. Along with mutagenesis and mass spectrometry analyses, the work provide insight into Fas mutations that cause autoimmune lymphoproliferative syndrome.

SKAP and Astrin form a heterodimer that localizes to spindle microtubules and to mature microtubule-kinetochore attachments during mitosis. Here, the authors identify molecular requirements for the inter-subunit interaction of SKAP and Astrin and kinetochore recruitment.

tRNA-dependent cysteine biosynthesis is catalyzed by the transsulfursome protein complex. Here, the authors use a multidisciplinary approach to structurally characterize the archaeal transsulfursome and propose a model for tRNA channeling in the complex.

The serine protease HTRA1 utilizes a "disintegration" mechanism involving its flexible PDZ domains to first loosen tau amyloid fibrils and subsequently disintegrating the fibrillar core structure for efficient proteolytic degradation.

Thorsten Wagner et al. present SPHIRE-crYOLO, a particle picking software for selecting particles from digital micrographs in cryoEM data. After training, the method automatically recognizes particles with high recall and precision, simplifying data pre-processing.