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SLCO2A1 (also known as OATP2A1) is responsible for the transport of eicosanoids, including prostaglandins (PGs), as well as of a subset of nonsteroidal anti-inflammatory drugs (NSAIDs). Here, structures of SLCO2A1 bound to PGs and to four widely used drugs elucidate the molecular basis for PG and drug recognition.

The role of mitochondrial supercomplexes in guiding redox proteins across membranes during energy conversion remains unclear. Here, authors integrate multiscale modeling and cryo-EM to examine mechanisms of electron transfer and energy conversion efficiency.

Betaglycan is a co-receptor for selective TGF-β family ligands. Here, the authors solve its structure in complex with TGF-β and the signaling receptors, which explains its ligand selectivity and reveals its mechanism in potentiating TGF-β signaling.

Several transmission-blocking vaccine candidates based on Pfs230 and Pfs48/45 are in clinical development, but it remains unclear whether they will demonstrate high efficacy. Here, the authors develop a stabilized chimeric antigen presenting potent epitopes from Pfs230 and Pfs48/45 in a single construct and demonstrate induction of transmission-reducing antibodies when female mice are immunized with the antigen in a self-assembling protein nanoparticle formulation.

The P2X4 receptor, an ATP-activated ion channel, plays a role in chronic pain, inflammation, and cancer. Authors in this work discover an extracellular allosteric binding site that interacts with anthraquinone derivatives, and is narrowed by ionic lock formation.

CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.

Influenza viruses carry their own RNAdependent RNA-polymerase that is highly conserved and a promising anti-viral target. Combining functional and structural data, Keown et al. characterise the inhibitory effect of nanobodies on 1918 pandemic H1N1 influenza strain polymerase complex and identify sensitive sites interfering with polymerase activity in vitro.

Borna disease virus 1 replicates and transcribes its negative sense RNA genome in the nucleus of infected cells. Here, the authors present the cryoEM structures of the large polymerase protein in complex with the tetrameric phosphoprotein, revealing the structural features that govern its activity.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

The cryo-electron microscropy structures of the full-length ectodomain of VAR2CSA in both ligand-binding and ligand-free states reveal the sequestration mechanism of placental malaria.

Structures of the human calcium-sensing receptor can be bound into complex with G proteins from three different Gα subtypes while maintaining G-protein-binding specificity.

Albicidin is a peptide antibiotic that has shown great promise for inhibiting DNA topoisomerase of fluoroquinolone-resistant Gram-negative pathogens, but its mode of action is not fully clear. Now, cryoelectron microscopy structures of albicidin–gyrase complexes provide detailed insights into the mechanism of this natural product.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Here, the authors use cryo-EM to solve the structures of seven potent human antibodies, and demonstrate in vivo protection in a liver burden assay, using chimeric Plasmodium berghei sporozoites expressing Plasmodium falciparum circumsporozoite protein.

Metazoans have evolved endocrine systems that signal through dimerized receptors in response to cognate hormones. These authors characterize a nematode homolog of such human receptors, presenting the cryo-EM structure of an asymmetric dimer that embodies properties of the human receptors.

Outer membrane protein TraT protects bacteria from secondary F plasmid conjugation. Here, the authors report cryo-EM structure of decameric cork-like TraT and its evolutionary history as a chromosomal gene that has been incorporated into multiple plasmid families.

Gasdermin D Cys191 is S-palmitoylated, and palmitoylation is required for pore formation.

In this work, the authors present structural and functional evidence of lipid exchange within the gram-negative Mla pathway, broadening our understanding of lipid transport in bacteria and providing insight into the mechanism of a unique ABC transporter.

Here the authors develop a ferritin-based protein nanoparticle vaccine candidate for SARS-CoV-2, and show induction of neutralizing antibodies to variants of concern, including Omicron BQ.1, in non-human primates after initial immunization and a booster dose.

Zeinert et al. provide cryo-EM structures of the E. coli Mg²⁺ importer MgtA: unexpectedly, this P-type ATPase is a dimer with an uncommon transmembrane ion-binding site and knotted N-terminus, which are functionally important features.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

The authors demonstrate how avian H5N1 influenza A virus polymerase interacts with human ANP32B to facilitate the replication of the viral genetic information in mammalian hosts, revealing insights into cross-species transmission.

Recurrent features in human antibodies targeting the influenza neuraminidase active site reveal a convergent strategy of receptor mimicry, providing structural insights that could guide the design of broad and effective influenza vaccines.

Structures of RNA polymerase of human and avian influenza A viruses reveal that the interface of the RNA polymerase dimer is required to initiate viral RNA synthesis in viral genome replication.

The synaptic vesicle protein 2 family are essential membrane proteins found in the brain that bind synaptotagmin and are targeted by anti-seizure medications. Structures reveal common features found in transport proteins, and the basis of ligand binding and selectivity.

Recent observations of silicic eruptions show that they can be both effusive and explosive at the same time. Here the authors use scaled experiments to demonstrate that magma in effusive eruptions will fracture during flow to the Earth’s surface, accommodating mixed eruption styles.

δ-Opioid receptors (δOR) are promising targets for pain management with reduced side effects. Here, the authors use a structure-based approach to design and characterize C6-Quino, a selective δOR partial agonist, highlighting its potential therapeutic relevance.

A standardized, realistic phantom dataset consisting of ground-truth annotations for six diverse molecular species is provided as a community resource for cryo-electron-tomography algorithm benchmarking.

Despite advances in GPCR structures and peptide design, creating high-affinity ligands remains a challenge. Here the authors develop a computational method, successfully identifying peptide-based molecules for KOR: their platform shows promise for streamlined GPCR ligand discovery.

The biogenesis of iron-sulfur proteins in eukaryotes is initiated by the mitochondrial core ISC complex. Here, the authors provide structural, biochemical and spectroscopic data to characterize sulfur transfer intermediates in the core ISC complex.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Cryo-electron microscopy and biochemical studies elucidate the read–write mechanisms of non-canonical PRC1-containing RYBP in histone H2A lysine 119 monoubiquitination and their roles in maintaining epigenetic inheritance.

Many neurotransmitters act on receptors coupled to GTP-binding G proteins. Here authors report the structure and activity of a mutant that locks the nucleotide-free and receptor-bound state of the G protein, leading to a rare neurological disorder.

A broadly neutralizing antibody (bnAb) response is required to combat SARS-CoV-2 variants of concern (VOCs). The authors isolated and characterized a large panel of sarbecovirus bnAbs from vaccinated individuals who had recovered from COVID-19, finding that many of these antibodies were able to neutralize all VOCs, including Omicron, and demonstrate prophylaxis in mice infected with diverse sarbecoviruses.

In this study, the authors present the cryogenic electron microscopy reconstruction of the Rpd3S complex engaged with a nucleosome. The corresponding model describes the interactions that facilitate histone deacetylation within gene bodies by the Rpd3S complex.

The cryo-electron microscopy structure of the filamentous hydrogen-dependent CO₂ reductase (HDCR) enzyme from Thermoanaerobacter kivui, together with enzymatic analysis and in situ cryo-electron tomography, provides insight into the high catalytic activity of HDCR.

nextPYP is a turn-key framework for single-particle cryo-electron tomography that streamlines complex data analysis pipelines, from pre-processing of tilt series to high-resolution refinement, for efficient analysis and visualization of large datasets.

Isotopic labelling and multi-omics experiments conducted in Biosphere 2 show how dry conditions reprogramme microbial metabolism.

Structural, functional and in silico analyses of the chloroquine-resistance transporter PfCRT of Plasmodium falciparum suggest that distinct mechanistic features mediate the resistance to chloroquine and piperaquine in drug-resistant parasites.

Structural studies of the itch receptors MRGPRX2 and MRGPRX4 in complex with endogenous and synthetic ligands provide a basis for the development of therapeutic compounds for pain, itch and mast cell-mediated hypersensitivity.

Vilazodone (VLZ) is a drug for the treatment of major depressive disorders that targets the serotonin transporter (SERT). Here, the authors combine pharmacology measurements and cryo-EM structural analysis to characterize VLZ binding to SERT and observe that VLZ exhibits non-competitive inhibition of serotonin transport and binds with nanomolar affinity to an allosteric site in SERT.

Active-state structures of the κ-opioid receptor in complexes with the G-protein heterotrimers G_i1, G_oA, G_z and G_g provide insights into the actions of hallucinogenic opioids and G-protein-coupling specificity at the κ-opioid receptor.

This comprehensive study of the most enigmatic serotonin receptor 5-HT_5AR includes lots of pharmacological investigations, inactive and active state structures with antagonist, partial agonist and full agonists. Also, a highly potent and selective antagonist was developed.

To fully understand the potential shortcomings of SARS-CoV-2 vaccination, it is necessary to delineate the properties of the antibodies elicited, during immunization, and also infection. Through investigation of the SARS-CoV-2 spike-reactive B cell repertoire, authors identify following infection, a subset of B cells enriched and almost exclusively target a non-neutralizing S2 epitope present in aberrant forms.

The mechanism of action of muscarinic receptor-based DREADDs, important chemogenetic tools in neuroscience and cellular signalling research, are described in molecular detail.

Most DNA-encoded library (DEL) syntheses are limited by the presence of sensitive DNA-based constructs. Here, the authors develop DOSEDO, a diverse 3.7 million compound DEL, generated through diversity-oriented synthesis that provides enhanced scaffold and exit vector diversity and gives validated binding hits for multiple protein targets.

New high-resolution cryo-electron microscopy structures of the HIV-1 envelope protein provide a detailed description and understanding of how the HIV-1 fusion machinery functions and how it changes its structure over time to convert from the pre-fusion to the fusion-intermediate conformation.