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The number of K⁺ occupied binding sites in the selectivity filter of potassium ion channels is still under debate. Here, the authors collect diffraction data on the K⁺ selective NaK channel NaK2K at a wavelength of 3.35 Å, close to the K absorption edge, revealing that all four binding sites in the selectivity filter are fully occupied by K⁺ ions.

Cryoelectron microscopy analyses of the counter-clockwise and clockwise states of the Salmonella Typhimurium C-ring reveal the structural bases for changes in rotation of the bacterial flagellum.

mBaoJin is a monomeric derivative of the bright and photostable green fluorescent protein StayGold. mBaoJin offers favorable photophysical properties for use in diverse protein tagging and subcellular labeling applications.

The EMDataResource Ligand Model Challenge aimed at assessing the reliability and reproducibility of modeling ligands bound to protein and protein–nucleic acid complexes in cryo-EM maps determined at near-atomic resolution. This analysis presents the results and recommends best practices for assessing cryo-EM structures of liganded macromolecules.

There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

In this work, the authors probe the efficacy of BWC0977, a bacterial topoisomerase inhibitor, in pre-clinical animal models, also demonstrating that BWC0977 is safe and well tolerated in healthy human volunteers, in a phase 1 trial.

Residues within the catalytic site of enzymes are important for activity, but whether more distant residues are also sensitive to mutation is unclear. Here, Leferink et al.show that mutation of residues in copper nitrate reductase that are 12Å away from the active site perturb enzyme function.

The analysis of radial velocity variations of O-type stars in the Small Magellanic Cloud reveals a large fraction of close binaries, suggesting that binary physics also plays a prominent role in the low-metallicity environment of the distant Universe.

An antibody that recognizes the F glycoproteins from Nipah and Hendra viruses can neutralize both viruses and recognizes a quaternary epitope in the prefusion F trimer, preventing conformational changes required for fusion.

In a quantum simulation of a (2+1)D lattice gauge theory using a superconducting quantum processor, the dynamics of strings reveal the transition from deconfined to confined excitations as the effective electric field is increased.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Tailed bacteriophages assemble empty precursor capsids known as procapsids that are subsequently filled with viral DNA by a genome-packaging motor. Here the authors present a structure-based analysis that suggests the signal for termination of genome packaging is achieved through a DNA-dependent symmetrization of portal protein.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

The Tousled-like kinase (TLKs) family belongs to a distinct branch of Ser/Thr kinases that exhibit the highest levels of activity during DNA replication. Here the authors present the crystal structure of the kinase domain from human TLK2 and propose an activation model for TLK2 based on biochemical and phosphoproteomics experiments.

Cryo-EM data and functional assays reveal how the actin-cross-linking protein filamin A interacts with F-actin, rationalizing human disease mutations in molecular detail.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Here, using cryo-EM, biochemistry and cell biology, the authors reveal the unique assembly, catalytic mechanism, multimodal substrate recruitment and regulation of the atypical ubiquitin ligase complex CUL9–RBX1.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

Embedding of a new engineered thermostable hydrolase into polymer materials enables the production of biodegradable and home-compostable plastics suitable for industrial packaging applications.

Using cryo-EM, authors reveal the structure and activation mechanism of GPR156, a class C orphan GPCR implicated in sound detection. They find that GPR156 is a transducer for phospholipid signaling and provide insights into the basis for its constitutive activation.

Cancer cells often acquire molecular patterns of fast-growing embryonic tissues to enable propagation and invasion, which distinguish tumour tissues from their healthy adult counterpart. Here authors develop antibody fragments which specifically target oncofetal chondroitin sulphate on the cancer cell surface and in the tumour stroma, with the antibodies achieving therapeutic effect in multiple mouse models in antibody drug conjugate and bispecific immune cell engager formats.

Centriole duplication is tightly regulated in vivo, but the underlying molecular mechanisms are incompletely understood. Here the authors use high-resolution structural and imaging methods to show that CEP85 directly interacts with STIL and mediates efficient centriolar targeting of STIL, PLK4 activation and centriole assembly.

The rod-shaped virus APBV1 is among the most thermostable viruses known. Here, Ptchelkine et al. determine its structure at near-atomic resolution, show that the DNA is packed as left-handed superhelix and identify extended hydrophobic interfaces that likely contribute to the extreme thermostability of the capsid.

KirBac channels are the bacterial homologs of mammalian inwardly rectifying potassium (Kir) channels. All available structures are closed at the helix bundle crossing, but the crystal structure of an open-state KirBac channel now indicates how opening of the primary activation gate may be physically coupled to a rotational twist in the cytoplasmic domain.

Schmidpeter and colleagues showed that anionic lipids bind to pacemaker ion channels and increase their activity by acting like keys that unlock salt bridges at the channel gates.

Here, the authors identify a small molecule degrader (XL44) for hRpn13 and solve the XL44-hRpn13 structure. XL44 induces apoptosis in myeloma cells with hRpn13 dependency and also targets KEN box proteins PCLAF and RRM2. Loss of hRpn13 and PCLAF abrogates XL44 restriction of cell viability.

Regulation of the actin cytoskeleton is essential for blood-brain barrier integrity and immune cell transmigration. Here, the authors show that the ion channel K2P2.1 regulates this process by shielding key signaling lipids and modulating actin dynamics.

Kainate receptors (KARs) contribute to excitatory neurotransmission, neuronal plasticity and neurological disorders. Here, Gangwar et al. present KAR structures in complex with channel blockers NpTx8, PhTx74, KukoA, and spermine, which become trapped inside the channel upon its closure.

Cellobiohydrolases (CBHs) are critical for natural and industrial biomass degradation but their structure–activity relationships are not fully understood. Here, the authors present the biochemical and structural characterization of two CBHs, identifying protein regions that confer enhanced CBH activity.

The authors developed a small molecule targeting the circadian regulator BMAL1, enabling dose-dependent modulation of gene expression for circadian-controlled genes and downregulation of inflammatory pathways in macrophages.

The human transferrin receptor 1 (CD71) is a transmembrane protein responsible for iron uptake. Here the authors present the 3.9 Å resolution cryo-EM structure of the CD71 ectodomain-human ferritin (H-Ft) complex and find that H-Ft binds a CD71 region different from the transferrin one that overlaps with the surface recognized by select pathogens.

RNA caps other than the 7-methylguanylate modification are generated by a distinct mechanism in which caps are added during, not after, transcription initiation through the use of non-canonical initiating nucleotides by RNA polymerases, a finding which has functional consequences.

This study reports the structure of lysosomal N-acetyltransferase HGSNAT providing insights into the mechanism of lysosomal transmembrane acetylation of heparan sulfate required for its catabolism.

Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Structures of the growing peptide chain on and off the ribosome reveal that the ribosome destabilizes the unfolded nascent chain, promoting the formation of partially folded intermediate states.

Using cryo-EM, Schmidt, Schulz, et al. solve the structure of the iron nitrogenase complex, which shows a unique architecture of alternative nitrogenases and suggests the G subunit to be involved in substrate channeling, stabilization of the cofactor and determining specificty among nitrogenase components.

The human type 1 insulin-like growth factor receptor (IGF-1R) is important for normal human growth and development. Here, the authors present the crystal structures of the IGF-1R ectodomain both in its apo form and in complex with its ligand insulin-like growth factor I and discuss the receptor activation mechanism.

The molecular basis of multidrug tolerance in chronic urinary tract infections is mediated by mutations in the N-subdomain-1 of the Escherichia coli HipA protein kinase.