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…or, Galileo's revenge…

The Pope's encyclical challenges incremental approaches that have dominated climate change discourse, and brings a much needed moral vision to the environmental movement. Social scientists are required to join this effort.

Phosphatidylinositol phosphates together with cholesterol bind at the interface between STING dimers, directly promoting high-order oligomerization.

Pentameric ligand-gated ion channels are modulated by anionic phospholipids. Here, by capturing an open-channel conformation of ELIC, the authors demonstrate the structural details of channel activation and a leaflet-specific mechanism for modulation by phosphatidylglycerol.

The study reveals the structure of ArnC, a membrane glycosyltransferase that modifies undecaprenyl phosphate with aminoarabinose (L-Ara4N), leading to polymyxin resistance. The structure of ArnC in two states and MD simulations provide insights regarding the catalytic cycle of the enzyme.

Researchers have resolved cryo-EM structures of the bacterial TamAB machinery in two distinct states: a non-hybrid and a novel hybrid barrel. These structures suggest each state enables a distinct function, facilitating outer membrane protein folding and phospholipid transport, respectively.

In this work, the authors report NMR lipids Databank to promote decentralised sharing of biomolecular molecular dynamics (MD) simulation data with an overlay design. Programmatic access enables analyses of rare phenomena and advances the training of machine learning models.

Despite the significance of high pressure in the story of life on Earth, our current understanding of biochemistry at high pressure is limited, primarily due to technological challenges associated with using pressure as an experimental variable. Here, the authors report in situ high-pressure magic-angle spinning solid-state nuclear magnetic resonance spectroscopy to study the fluidity of model microbial membranes at pressures up to 28 MPa, showing a stoichiometric effect of lipids in the membrane on the phospholipid lateral diffusion at high pressure.

Assembling synthetic plant cell is difficult due to the presence of primary cell wall. Here, the authors describe the assembly of lipid-containing bodies that can be coated with cellulose and pectin, and show how these so-called plantosomes can be manipulated by changing surrounding milieu.

The Pope, Smith and Kohler glaciers in West Antarctica have exhibited faster than expected retreat rates in recent years, according to grounding-line observations from satellite radar interferometry.

Energy coupling factor (ECF) transporters are responsible for the uptake of micronutrients and consist of an integral membrane unit, the S-component, which confers substrate specificity. Here, authors present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter.

Bacterial resistance to polymyxin antibiotics is conferred by enzymes such as phosphoethanolamine transferases, which add positively charged phosphoethanolamine to lipid A. Here, the authors present the structure of one such enzyme in its liganded form, and propose an enzymatic mechanism that may be generally applicable to other phosphoform transferases.

In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship between environmental antigen exposure and subsequent allergy.

Lipopolysaccharides (LPSs) in the outer membrane of Gram-negative bacteria play key roles in the microbial interactions with animals and plants. Here the authors identify a unique LPS with a covalently-attached hopanoid moiety that contributes to membrane stability in a bacterial symbiont of legumes.

The serotonin transporter (SERT) is a key antidepressant target. Here, authors present a cryo-EM structure where the antidepressant vilazodone spans the main SERT binding site toward a secondary pocket and provide further insights into ligand binding.

Lipid dynamics are analyzed in a model for the mitochondrial inner membrane using coarse-grained molecular dynamics. The model displays biological scales of curvature where strong partitioning of cardiolipin to negative curvature regions is observed.

He, Teng and Yang et al. report how metformin, the widely used antidiabetic drug, inhibit its target, the respiratory complex I, through a distinct state-dependent, inhibitor trapping mechanism, thus providing the molecular basis for its superior clinical tolerance.

Neurological processes from vision to cognition rely on precise control of ion channels, particularly GABAA receptors. Here, the authors report structures of a ρ1 GABAA receptor with naturally occurring steroids, revealing their specific interactions and suggesting approaches to understand and develop drugs.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Phox homology (PX) domains are membrane interacting domains that bind to various lipids. Here authors screen all human PX domains systematically for their phospholipid preferences and define four classes and provide the basis for defining and predicting functional PX-membrane interactions.

Interpretation of lipid-like densities in cryo-EM structures of membrane proteins is challenging. Here authors present LipIDens, enabling molecular dynamics analysis of protein-lipid interactions.

Bacterial O antigen polysaccharides play a role in innate immune response evasion. Here, the authors uncover the ATP-bound structure of the Aquifex aeolicus WzmWzt O antigen ABC transporter, shedding light onto the mechanism of lipid-linked polysaccharide translocation.

The asymmetric distribution of lipopolysaccharide (LPS) on the surface of the bacterial outer membrane is essential and crucial for antibiotic resistance. Here, authors characterize the LPS translocon holo-complex, LptDEMY, uncovering conformational translocon state transitions that might explain how LPS is assembled at the outer membrane surface.

Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.

In the healthy heart, the β₂ adrenergic receptor (β₂AR) signals through G_s and G_i proteins but the mechanism underlying G protein selectivity is not fully understood. Here, the authors show that membrane charge and intracellular cations modulate the β₂AR−G_i3 interaction.

This paper explores how voltage-gated potassium channels can plug the pore to prevent the conductance of ions during inactivation.

This study reveals that an outer membrane protein from the predator Bdellovibrio bacteriovorus forms a pentameric assembly that traps a lipid monolayer within. This allows the discovery of two superfamilies, distributed across a wide range of bacteria, likely to adopt a similar architecture.

The tumor environment is nutrient deficient. Here the authors show that early availability of methionine is critical for optimal T cell activation and prevents T cell dysfunction, and that dietary methionine can improve the efficacy of cancer immunotherapy in mice.

The dopamine transporter is responsible for termination of neurotransmission through Na⁺-driven reuptake of neurotransmitter from the extracellular space. Here authors use hydrogen-deuterium exchange mass spectrometry to monitor Na⁺- and dopamine-induced conformational dynamics of the dopamine transporter.

The serotonin transporter (SERT) is responsible for re-uptake of serotonin into the presynaptic neuron and plays a key role in synaptic transmission. Here, the authors use hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs.

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.

The insertion and folding nascent or fully synthesized polypeptides into membranes is assisted by insertases. Here, the authors use a range of biophysical approaches to provide molecular details of how the transmembrane insertase YidC facilitates the insertion a protein into a phospholipid membrane.

KtrAB is a major potassium uptake system that has been linked to the pathogenesis of many infectious bacteria. Here the authors show that KtrB from Vibrio alginolyticus contains an intrinsically disordered N-terminus that is key to its regulation.

The ρ-type GABAA receptors are potential therapeutic targets in several neurological conditions. Here, authors elucidate interactions of it with three therapeutic drugs, offering mechanistic insights and a prospective basis for further pharmaceutical development.

Cryo-EM structures of the full-length Junin virus and Machupo virus spike glycoprotein complexes stabilized in the prefusion conformation. Analyses reveal features that regulate glycoprotein pH-dependent membrane fusion activity.