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When the antibiotic erythromycin is bound to the ribosomal exit tunnel, ErmBL peptide translation stalls and allows translation of the downstream methyltransferase ErmB. Here the authors combine cryo-EM and molecular dynamics simulations to identify the underlying basis for the inhibition of peptide bond formation that results in ribosome stalling.

Water is vital for ion transport in anion exchange membranes (AEMs). Here, the authors used electrochemical impedance, ultrafast spectroscopy, and molecular models to reveal how water arrangements affect bromide ion transport in state-of-the-art AEMs, offering insights for better membrane design.

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.

Circulating metabolites reflect complex disease risk and are shaped by diverse genetic factors. Here, the authors show widespread pleiotropy across 249 metabolic traits, identify rare variant and sex-specific effects, and implicate lipid-related pathways in metabolism.

Here the authors use NMR, SAXS and MD simulations to characterise the structure of proteusin peptides, which are atypically long RiPP substrates. They show a small, unstructured region in the proteusin leader is sufficient for its interaction with a halogenase that brominates the terminal tryptophan residue.

The fibupeptide lugdunin has shown activity against antibiotic-resistant bacteria. Here, authors disclose its mechanism of action in lipid membranes and demonstrate that it assembles into nanotubes facilitating the translocation of monovalent cations.

Genetic factors that influence human height encompass rare monogenic variants as well as common and rare polygenic variants. In this Review, Bicknell et al. summarize our current understanding of the genetic underpinnings of human stature and link these genes to common developmental and cellular pathways that affect skeletal growth.

Photoreceptor proteins utilise biological chromophores to regulate a large range of cellular processes in response to light. Here the authors identify and characterise a sub-family of multi-centre photoreceptors, termed photocobilins, that not only utilise B₁₂ but also contain biliverdin (BV) as an additional chromophore.

Translation of RAPP (Arg-AlaPro-Pro) motifs induces ribosome stalling. Here, structures of RAPP-stalled ribosomes reveal that RAPP motifs short circuit the ribosomal peptidyltransferase activity to induce stalling.

Material from the Hokioi crater on asteroid Bennu experienced space weathering and suggests microcratering plays a more active role on carbonaceous bodies than initially thought, according to a study of OSIRIS-REx asteroid return samples.

Bacteriophage repressor proteins downregulate viral lytic gene expression. Herein, the authors present the X-ray crystal structure of a monomeric repressor that binds an asymmetric DNA sequence using two independent domains.

Here, the authors identify mechanisms of glycosylation of intrinsically disordered regions present in streptococci membrane proteins, uncovering a functional role for glycosylation in Streptococcus mutans chaperone PrsA.

Amine headgroups in ionizable lipids drive the immunogenicity of lipid nanoparticles by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation.

Host proteins CPSF6, NUP153, and SEC24C are vital for HIV-1 infection. They bind to the viral capsid protein and contribute to shuttling of virions through the cytoplasm (SEC24C), import into the nucleus (NUP153 and CPSF6) and subsequent trafficking to preferred integration sites (CPSF6). Here, Wei et al. combine structural, biochemical and virological assays to emphasize the importance of prion-like low complexity domains surrounding short phenylalanine-glycine regions in binding and increasing the avidity when interacting with viral capsid.

Glycine receptors are channel receptors mediating signal transduction between neurons that transit between resting and open states upon neurotransmitter binding. Here, the authors illuminate a progressive transition of opening by combining voltage-clamp fluorometry and molecular dynamics.

Two highly charged disordered human proteins phase-separate into viscous complex coacervates while retaining their rapid conformational dynamics through pico- to nanosecond exchange of short-lived side-chain interactions.

BAX and BAK are proapoptotic proteins that directly mediate mitochondrial outer membrane permeabilization (MOMP). Here, lipidomics and other data provide insight on how local lipid environment affects BAX and BAK function during apoptosis, suggesting that unsaturated lipids promote BAX pore activity.

Ceramides are lipids that act directly on mitochondria to trigger apoptosis, but the underlying mechanism remains largely unclear. Here authors use a photoactivatable ceramide probe combined with a computation approach and functional studies to identify the voltage-dependent anion channel VDAC2 as a direct effector of ceramide-mediated cell death.

Psoriasis is a partially heritable skin disorder, the genetic basis of which is not fully understood. Here, the authors use genome-wide association meta-analysis to discover psoriasis susceptibility loci and genes, which encode existing and potential new drug targets.

Editor summary: A native-mass-spectrometry-based approach analyzes integral membrane protein–lipid complexes directly from near-physiological membrane conditions, providing information about protein oligomeric states, lipid identities, and membrane properties.

Nucleocytoplasmic Large DNA Viruses (NCLDV) that infect algae encode two distinct families of microbial rhodopsins. Here, the authors characterise two proteins form the viral rhodopsin group 1 OLPVR1 and VirChR1, present the 1.4 Å crystal structure of OLPVR1 and show that viral rhodopsins 1 are light-gated cation channels.

Using a combination of methods, the mechanism of the antibiotic teixobactin is revealed.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

The chaperone SurA is involved in outer membrane protein (OMP) biogenesis in Gram-negative bacteria, but its mechanism of action is not fully understood. Combining mass spectrometric, biophysical and computational approaches, the authors here show how the conformational dynamics of SurA facilitate OMP binding.

Nerve injury activates microglia to remove spinal synapses, disrupting spinal sensory processing and contributing to chronic pain. Blocking complement protein C1q preserves synapses, highlighting a potential therapeutic target for neuropathic pain.

Analysis of policies for promotion criteria to full professor from academic institutions and government agencies worldwide reveals considerable variation in assessment practices, particularly between the Global North and South.

The collective nature of reorientational dynamics in water remains poorly understood. Here, the authors show that large angular fluctuations require a highly cooperative dynamics involving correlated motion of many water molecules in the hydrogen-bond network that form spatially connected clusters.

The respiratory complex I (NADH:ubiquinone oxidoreductase) is a large redox-driven proton pump that initiates respiration in mitochondria. Here, the authors present the 3.0 Å cryo-EM structure of complex I from mouse heart mitochondria with the ubiquinone-analogue inhibitor piericidin A bound in the active site and with kinetic measurements and MD simulations they further show that this inhibitor acts competitively against the native ubiquinone-10 substrate.

Here, using a multisystem approach, the authors characterize the impact of Moderate Acute Malnutrition (MAM) on the gut-brain axis and its effects on cognitive and microbiome development in one-year-old children from Dhaka, Bangladesh, finding relationships between faecal microbiota (specifically the species Rothia mucilaginosa, Streptococcus salivarius, and Bacteroides fragilis), plasma odd chain fatty acid concentrations, brain activity, and behavioral measurements.

Bacterial cell shape is dependent on the formation of the extracellular sugar polymer called peptidoglycan. Here the authors describe RodA-PBP2, the enzymatic core of the elongasome, which is the complex responsible peptidoglycan synthesis, and utilize an integrated approach to investigate the mechanism of peptidoglycan biosynthesis.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Characterization of the conformation landscape of the bacterial ABC transporter CydDC reveals that this heterodimeric protein complex is a long-sought heme transporter essential for the functional maturation of bd-type cytochromes.

Topical microbicide combined with vaccine effectively prevents infection of female macaques with simian immunodeficiency virus.

Cryo-electron microscopy structures of the human calcium-sensing receptor in complex with G_i and G_q proteins reveal how this receptor activates distinct G protein subtypes and how its function is modulated by a variety of ligands.

Using single-molecule imaging and manipulation, the authors show linker histone H1 preferentially forms phase-separated droplets with single-stranded nucleic acids over double-stranded DNA and nucleosomes, suggesting a noncanonical nuclear function.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

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.

Macrolides and ketolides antibiotics selectively interfere with the translation of a specific subset of proteins. Here the authors show how the macrolide erythromycin and the ketolide telithromycin interplay with the nascent polypeptide chain to arrest translation.

IFITM3 shifts upon phosphorylation from acting as an antiviral effector to being a scaffold for PIP3 and thereby amplifies PI3K signalling, which can be co-opted for malignant transformation in B cell leukaemia and lymphoma.

RNA-guided CRISPR-associated transposases (CAST) are natural systems with broad potential in biotechnology. Here, the authors report compact type V-K CAST discovered from genome-resolved metagenomics and demonstrate targeted integration of a large transgene to a safe-harbor site in the human genome.

Here the authors present the high-resolution structures of 17 antibiotics bound to Escherichia coli ribosomes, which may inform the development of new antibacterial agents. Their results unveil a conserved manner of antibiotic binding to the ribosome, including ordered water molecules.