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Single-particle cryo-EM is a powerful method for macromolecular structure determination. Here the authors demonstrate that Ewald sphere curvature correction, sub-Angstrom pixilation and per-particle CTF refinement can improve map quality and resolution and present the 1.86 Å cryo-EM structure of an adeno-associated virus serotype 2 variant.

Long-range interactions are challenging for machine learning interatomic potentials (MLIPs). Here, authors show that, by just learning from energies and forces, MLIPs can accurately capture electrostatics and predict atomic charges.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

Drugs that rescue function of episodic ataxia 1 (EA1) mutant potassium channels are lacking. Here, Manville et al identify and describe the molecular basis for Native American botanical ataxia remedies that directly rescue EA1 mutant channels.

Using activity-based chemical probes, oncogenic IDH1-R132H but not the wild type was found to acquire a unique autopalmitoylation at C269. This mutant-specific modification is critical for the enzyme’s abnormal activity in cancer.

Optical diffraction tomography (ODT) enables 3D imaging of transparent samples but is limited by coherence-related artifacts. We present Gradient ODT, which uses partially coherent light to achieve high signal-to-noise imaging and introduces refractive index gradients as a new, highly sensitive 3D contrast mechanism.

Drug transport by ABC exporters has been associated with multidrug resistance in cancer and bacterial infections. Here, we describe structures of an ABC heterodimer that illuminate drug transporter interactions and the role of lipids in facilitating drug expulsion across membranes.

Serial femtosecond crystallography and the use of X-ray free-electron lasers (XFEL) promise to revolutionize structural biology. Here, the authors describe refinements that reduce the redundancy required to obtain quality XFEL data and report a 1.75-Å structure—not obtainable by synchrotron radiation—using less than 6,000 crystals.

Most schemes for three-dimensional (3D) structure determination of an object require multiple measurements over various orientations, or a means of scanning it section by section. A 3D imaging modality, termed ankylography, is now presented that under certain circumstances enables complete 3D structure determination from a single diffraction measurement. This approach could find broad applications in the physical and life sciences.

Multidrug efflux pumps help bacteria survive stress and promote antibiotic resistance. Here, authors define the molecular detail of an anaerobic-connected pump MdtF uncovering acid-responsive activity which may enable toxin control in certain niches.

Lithium metal batteries suffer from instability under extreme temperatures. Here, the authors develop a weakly solvating electrolyte based on an asymmetric ether that builds bi-layer electrode-electrolyte interfaces, enabling Li | |SPAN batteries to operate reliably from −40 °C to 60 °C

Here, authors provide a molecular view of a clustered saccharide patch on mucins as recognized by a bacterial binding module. This work provides insights into how microbes can remain attached to mucins in the mucus while grazing on their glycans.

The textile industry’s reliance on synthetic dyes is an important source of greenhouse gas emissions. Here the authors describe a process involving sustainable solvents that allows the extraction, purification, and reuse of dyes, as well as the recycling of dye-free fabrics.

Differences among homologous receptor proteins complicate target-specific drug design. Here, authors develop an interpretable dynamic machine learning model DRUMBEAT to identify amino acid residues enabling distinct conformational transitions in proteins.

Vitamin K-dependent carboxylation is vital for human health. Here, authors present cryo-EM structures of the relevant γ-glutamyl carboxylase, uncovering substrate recognition, processive modification, and a bicarbonate-mediated CO₂ fixation mechanism.

The mechanism of superconductivity in layered kagome metals remains unclear, however its coexistence with charge order suggests exotic interpretations. Here the authors study the vortex lattice in the superconducting state of Ta-doped CsV₃Sb₅ with suppressed charge order, suggesting conventional pairing.

Water-vapor interfaces have been studied with many techniques, yet open questions persist about their electronic and molecular structure. Here, the authors demonstrate the application of soft x-ray second harmonic generation to study the water surface by leveraging attosecond pulses at the LCLS and a flat liquid sheet microjet, providing insights on the H-bond structure.

Here they show that mitochondria-localized NEK7 couples mitochondrial complex II subunit SDHB to maintain the homeostasis of electron transport in hepatocytes, thereby impeding the progression of liver fibrosis.

Myocardial infarction triggers inflammation driven by immune cell reprogramming, but the epigenetic regulators involved remain unclear. Here, the authors show that histone acetyltransferase 1 enhances postinfarction inflammation by promoting histone succinylation in monocytes.

Bacterial mechanosensitive channel YnaI opens at near-lytic membrane tension. Here, authors show that YnaI remains open to a much lower membrane tension than required for its activation and evolved to respond to slow changes in membrane tension.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

Despite frequent AKT/mTOR pathway activation in patient’s rhabdomyosarcoma (RMS), success of AKT inhibitors in the clinical has been limited. Here, using RMS patient-derived models, the authors demonstrate that the efficacy of the AKT inhibitor, ipatasertib, is in part due to its off-target effects on PRKG1, identifying PRKG1 as a potential biomarker for ipatasertib response.

The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. Here the authors combine molecular dynamics simulations and smFRET in cells, to investigate the early stages of MET activation.

Natural antimicrobial peptides and enzymes are good candidates for application but suffer from low stability. Here, the authors report on biomimetic self-assembling peptides which mimic both antimicrobial peptide and enzyme functionality, demonstrating application against fungal infection.

Monoclonal antibodies targeting the conserved neuraminidase catalytic site mimic sialic acid and use coordinated water molecules to inhibit diverse influenza A and B viruses, including H5N1, providing broad prophylactic protection in mice.

Ligands that activate GPCRs generally do so by stabilizing a particular conformation of the transmembrane helices. Here, the authors reveal a distinct activation mechanism where a ligand instead stabilizes a particular intracellular loop conformation.

Description of the cryo-EM structures of the parathyroid hormone type 1 receptor associated with G_q reveals two distinct extracellular conformations with N-glycans stabilizing a ligand-tilted conformation.

Distal mutations, though far from the active site, enhance Kemp eliminase catalysis by tuning conformational dynamics that facilitate substrate binding and product release, thereby promoting the full catalytic cycle.

By combining the sensitivity and high temporal resolution of phase imaging with the specificity and high spatial resolution of fluorescence microscopy, a 4D microscope is demonstrated that visualizes in three dimensions the fast cellular processes in living cells at up to 200 Hz.

Mixtures of peptides and nucleic acids tend to demix and form coacervate droplets. Here, the authors show that even short peptides and oligonucleotides form droplets. DNA and RNA impart different properties to these protocells – stability, fluidity and the potential to host RNA chemistry.

PROTACs induce degradation by bridging a target protein and E3 ubiquitin ligase. Here, authors show that protein interface frustration correlates with cooperativity, offering a structural metric to prioritize PROTAC candidates prior to synthesis.

Mirror image peptides are of interest for a range of biotechnology applications. Here, the authors report on the creation of fully functional mirror-image transmembrane pores made of D-amino acid peptides, which have potential in nanopore sensing technologies and cancer therapies.

The location of EGFR exon 20 loop insertions (EGFRex20ins) has been shown to alter sensitivity to lung cancer therapy. Here, the authors report the results of the ZENITH20 clinical trial investigating poziotinib (EGFR TKI) in lung cancer patients and, combining with a similar trial, investigate how structural differences due to location of EGGFRex20ins alters sensitivity to EGFR TKI.

Desmosomes are adhesive junctions in tension prone tissues. Here, the authors show that cytoskeletal forces alter the conformation of desmoplakin, a key desmosomal protein, and propose this may enable the desmosome to sense and respond to mechanical stimuli.

Potential ligand class-dependent differences in STING activation have both evolutionary and therapeutic implications. Here, the authors observe a unique oligomerization state of STING with an open-LBD ligand, suggesting additional regulatory mechanisms involved in activation by this ligand class.

Here the authors report SBCG2 an update to the neural network based, Shape-Based Coarse Graining (SBCG) approach for creating coarse grained molecular topologies with atomistic detail. They show how SBCG2 can reduce the computational costs of simulating very large assemblies like the HIV-1 capsid allowing simulation on commodity hardware.

Garnet-type LLZO electrolytes are considered among the most promising solid-state electrolytes for all-solid-state batteries; however, numerous challenges need to be addressed before they are integrated into a cell. By precipitating amorphous zirconium oxide onto grain boundaries, increased ionic conductivity is observed and dendrite growth is suppressed.

BamA is the catalytic core of the BAM complex, which inserts proteins into bacterial outer membranes. Here, the authors show that hinge flexibility between BamA’s β-barrel and POTRA domains is vital, demonstrating how evolution has fine-tuned the BamA sequence and structure for function.

An algorithm has been developed that can provably predict the lowest energy structure of crystalline materials using a combination of combinatorial optimization and integer programming.

IP6 is a critical host cofactor for HIV-1 assembly and infectivity. In this study, the authors uncover the structural basis by which HIV-1 adapts to a deficiency in IP6 packaging through a G225R mutation at the C-terminus of the capsid protein.

High-resolution microscopy allows imaging of information on the atomic scale. Here, by combining precession electron diffraction with scanning transmission electron microscopy, the authors demonstrate an efficient, alternative technique to determine the three-dimensional orientation of materials.

Rational design of protein labelling sites for ¹⁹F NMR experiments using AlphaFold predictions and molecular dynamics simulations enables simple, direct analyses of protein structure and interactions in vitro and in-cell.