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Species homogenisation driven by land-use intensification is threatening many taxa globally. Here, the authors find that for arthropod communities in Central Europe, managed grasslands are the most affected land-use type, while there is a strong distance–decay relationship in settlements and arable fields, meaning that these support heterogeneous communities between locations.

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.

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.

Biased signaling in κ-opiod receptors (KOR) offer an attractive strategy for pain management. Here the authors identify determinants of KOR signaling bias using structural methods in combination with molecular dynamics simulations.

Cellulose is synthesized as microfibrils of β-1,4-linked glucan chains arranged in a crystalline lattice. Here Ye et al. use grazing incidence wide angle X-ray scattering to show that cellulose crystals are preferentially orientated parallel to the plant cell wall, rather than as twisting microfibrils as previously hypothesized.

This study reveals the structural basis of auxin import by the AUX/LAX family. LAX3 binds auxin as well as herbicides via a proton-coupled mechanism, which offers insights into hormone recognition that is essential for lateral root growth.

The SpyTag/SpyCatcher protein ligation technology is valuable in many applications, but few methods exist for controlling reactivity. Here the authors report a method for controlling SpyCatcher activity via S-thiolation of engineered cysteines, demonstrating the value of their technology for the rapid generation of bispecific antibodies.

PIN transporters are key players in distributing phenoxyacetic acid herbicides. Mutagenesis and cryo-EM structures elucidate substrate specificity and transport mechanisms, paving the way for improved synthetic auxin development and herbicide-resistant crops.

Piezoelectric materials which are non-toxic and eco-friendly are of interest. Here, the authors report on the creation of collagen-mimetic peptides which can be self-assembled into piezoelectric materials and study the design characteristics required for optimized power generation.

Epidermal growth factor receptors have been shown to oligomerise upon binding to their cognate ligands. Here, the authors use biochemical, biophysical and cell biology techniques to analyse the structures of these oligomers, and argue that these formations are required for signalling.

Structural analysis of the human choline and ethanolamine transporters FLVCR1 and FLVCR2 clarifies the mechanisms of transport, the conformational dynamics of these proteins and the disease-associated mutations that interfere with these processes.

Work by Klyshko and Kim et al. lays the foundation for simulating pump-probe experiments and demonstrates how the dynamic behaviour of proteins extends to the crystal environment, emphasizing the need for an ensemble view in understanding functional motions.

Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal structures of the MLKL pseudokinase domain in two distinct conformations. By combining their structural data with cell signalling assays and MD simulations they provide evidence that endogenous MLKL preassociates with its upstream regulator RIPK3, and that MLKL disengages from RIPK3 following the induction of necroptosis.

Complexes that form between oppositely charged polyelectrolytes may be solid or liquid. Here, Perry et al.show that chirality in polypeptides can determine the state of those complexes based on a propensity for hydrogen-bond formation.

Combining expansion microscopy with super-resolution radial fluctuations captures the morphology of single proteins.

The role of the A-site (A=Li, Na, Cu and Ag) cation chemistry on ionic conductivity is studied in A₂ZrCl₆ solid-state electrolytes (SSEs). This work explores the limits of conductivity in halide SSEs, providing new avenues for materials design.

Structural studies of the native transmembrane channel-like protein 1 (TMC-1) mechanosensory transduction channel complex of Caenorhabditis elegans reveal the subunit composition and the roles of protein–membrane interactions in the conversion of mechanical force to ion channel activity.

Gram-negative bacteria assemble biofilms from amyloid fibres, which translocate across the outer membrane as unfolded amyloid precursors through a secretion system. Here, the authors characterise the structural details of the amyloid transporter FapF in Pseudomonas.

Zhang and colleagues report that multicellular clusters of circulating tumor cells are more resistant to killing by natural killer (NK) cells through altered NK ligand expression, resulting in polyclonal metastases.

Engineering enzymes to accept noncanonical cofactor biomimetics is difficult. Here, the authors establish a self-sufficient growth selection method and demonstrate its application in engineering the Lactobacillus pentosus NADH oxidase to efficiently recycle reduced nicotinamide mononucleotide (NMNH).

Mutation associated neoantigens are a family of highly specific therapeutic targets for the treatment of cancer. Here, the authors describe the cryo-EM structure of an antibody bound to a neoantigen complex providing insights into the specificity of the antibody.

Cryo-electron microscopy structure, molecular dynamics and biochemical analyses of the SHOC2–PP1C–MRAS complex demonstrate the dependence of the complex formation on RAS–GTP and identify the determinants of RAS isoform preference for SHOC2–PP1C and specificity of the complex for RAF dephosphorylation.

The antidepressant vortioxetine affects rodent and human 5-HT₃ receptors differently. López-Sánchez et al. use a variety of methods, including structure determination of vortioxetine-bound human and mouse 5-HT₃ receptors, to reveal the basis of these differences.

This study reveals the association of cholesterol with the Zika virus prM protein. It highlights the role of cholesterol during virus entry and assembly and shows the incorporation of cholesterol into the viral envelope.

SARS-CoV-2 main protease adapts a disulfide bonded inactive state to escape oxidative stress. Here, the authors report a crystal structure of an inactive conformation of the enzyme achieved through a H163A mutation, and the mechanistic details of conformational changes using atomistic simulations.

While dimethylarginine dimethylaminohydrolase 1 (DDAH1) is known to metabolize the endogenous inhibitor of nitric oxide synthases, asymmetric dimethylarginine (ADMA), the function of DDAH2 has remained controversial. Here, the authors present several lines of evidence that DDAH2 does not hydrolyze ADMA.

Thylakoid K⁺/H⁺ exchange by KEA3 optimizes photosynthesis during light fluctuations. Here, the authors show that a combination of stromal pH, ATP, ADP and NADP⁺, NADPH induces structural re-arrangements required for KEA3 regulation in vivo.

A study using cryo-electron microscopy has determined the structure of the human dopamine transporter with bound cocaine, revealing molecular details about neurotransmitter transport and how it is affected by neuropsychiatric drugs.

Fluorescent sensors that are responsive only in a specific subcellular location have remained elusive. Now, a chemogenetic sensing platform has been developed to sense glutathione in a user-defined organelle of interest. These tools enable quantitative studies of subcellular glutathione homeostasis using visible or near-infrared wavelengths.

HGF/c-MET upregulation is frequent in bladder cancer. Here, the authors show that HGF induces EMT and invasion by stabilising TGFβ receptor through inhibition of the SMURF2 ligase, and the combined blockade of MAPK and TGFβ pathways suppresses HGF-mediated bladder cancer progression.

Fluorescent proteins can report on many cellular variables. Here, authors develop a method for reporting high local densities, and use it to show that density distribution of heterochromatin in mouse embryonic stem cells are not in a liquid phase.

An integrated structural biology approach uncovers the structural complexity of the intrinsically disordered region (IDR) within the TRPV4 ion channel. Multiple stimulatory and inhibitory elements were identified within the IDR that modulate channel activity in a lipid-dependent manner.

Crystal structure of the Plasmodium falciparum hexose transporter PfHT1 reveals the molecular basis of its ability to transport multiple types of sugar as efficiently as the dedicated mammalian glucose and fructose transporters.

The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Here, authors present a cryo-EM structure and biochemical studies of secretin binding to the SecR:Gs complex which show that interactions between peptide and receptor were dynamic.

Cryo-EM structures of human SERINC5 and its fly orthologue, along with extensive functional analyses, reveal the protein architecture and identify regions important for HIV-1 restriction.

How different oncogenic Akt mutants can affect the response to Akt inhibitors is currently unclear. Here, the authors analyse somatic mutations of Akt1-3 isoforms in several human cancers, investigate their oncogenic effects and therapeutic relevance in vitro and confirm some of their data in a clinical trial testing the AKT inhibitor capivasertib in patients with solid tumors harboring AKT alterations.

The necroptotic cell death pathway involves signaling through pseudokinases. Here the authors define the structural determinants of species specificity in necroptosis signaling mediated by the essential necroptotic effector pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL).

A study reports the detection and characterization of SARS-CoV-2-like viruses in Laotian cave-dwelling bats that are also demonstrated to infect human cells through the ACE2 pathway.

Cryo-EM and molecular dynamics simulation analysis of peptide variants of GLP-1 and exendin-4 reveal distinct receptor conformers with unique modes of peptide–receptor engagement.

Previously, peptide selectivity in the VPAC receptor family of GPCRs was poorly understood. Here, authors combine cryo-EM and MD data to understand binding and selectivity of VPAC1R and PAC1R peptide agonists that can guide future drug development.

Although the TMPRSS2-ERG gene fusion is the most common alteration in human prostate cancer, its involvement in disease progression remains unclear. Here, the authors demonstrate that ERG is methylated by Enhancer of zest homolog 2 leading to enhanced transcriptional and oncogenic activity.

IFNγ-inducible guanylate binding proteins (GBPs) recognize the Toxoplasma gondii vacuole during infection. Here, the authors report that inducible nitric oxide synthase (iNOS) is necessary for efficient parasite clearance by GBPs and that reactive nitrogen species produced by iNOS lead to nitration of the parasite vacuole and collapse of the intravacuolar network space, preventing parasite escape from GBP targeting.

Hyper-activated STAT5B and its disease-causing variants are of interest as cancer drug targets. Here the authors combine cell based studies, X-ray crystallography, biophysical experiments and MD simulations to structurally and functionally characterize the STAT5B^N642H mutant found in aggressive T-cell leukemia and lymphomas and find that it has an increased affinity for self-dimerization.

Peptide self-assembly is a hierarchical process which includes forming β-sheets but the formation of high ordered structures remains largely unexplored. Here the authors report on a super-secondary structural template, based on well-defined hydrogen bonds by rational design and assembly of short peptides

Peroxisome proliferator-activated receptor gamma (PPARγ) is a target for insulin sensitizing drugs. Here the authors combine NMR, X-ray crystallography and MD simulations and report a structural mechanism for eliciting PPARγ inverse agonism, where coactivator binding is inhibited and corepressor binding promoted, which causes PPARγ repression.