376 papers
This study systematically characterizes the ability of various viral and cellular internal ribosomal entry sites (IRESes) to drive translation in synthetic circular RNAs across human cells and improved cell-free systems, providing critical insights for optimizing circRNA-based therapeutics.
This study extends previous findings on Nurr1-RXR to the Nur77-RXR heterodimer, revealing that while its activation involves both classical and non-classical dissociation mechanisms, a functionally diverse ligand set is essential to fully elucidate these pathways and determine if LBD heterodimer dissociation is a shared mechanism across NR4A-RXR complexes.
This study reveals that the bile salt glycocholate induces ToxS homodimerization through a strand-swapped mechanism, providing a structural model for how the ToxRS system senses bile to regulate virulence in *Vibrio* pathogens.
This study utilizes multiscale simulations to reveal that hydrogen-bonding changes within the active site, driven by mutations in the 5-6 loop, alter the dynamics and efficiency of imipenem deacylation and binding, thereby explaining the distinct hydrolytic activities observed among OXA-48 variants.
This study reveals that the catalytic efficiency of conserved metabolic enzymes does not follow a universal trend based on organismal complexity, but instead exhibits enzyme-specific and pathway-dependent variations driven by distinct context-specific selection pressures related to metabolic demand and regulatory needs.
This study presents high-resolution cryo-EM structures of Photosystem I from a *Synechocystis* Δ*menB* variant containing alternative quinones, revealing unexpected asymmetry in quinone binding and exchange between the A1A and A1B sites and providing new insights into cofactor selectivity and metabolic plasticity.
This study presents the structural analysis of three tetrameric crystal structures of *Trichomonas vaginalis* pyrophosphate-dependent phosphofructokinase (TvPPi-PFK), revealing conserved catalytic motifs, unexpected ATP and sugar phosphate binding sites at the dimer interface, and validating the enzyme's potential as a drug target for trichomoniasis.
This study introduces ThermoTargetMiner, a comprehensive database generated using the Proteome Integral Solubility Alteration (PISA) assay that maps the proteome-wide target landscapes of 67 lung cancer therapeutics, identifying novel pro-target candidates and validating specific drug mechanisms to advance lung cancer research.
This study demonstrates that non-fibrillar prion protein oligomers and transient assembly intermediates can store and transmit structural folding information through a modular mechanism involving a -sheet-rich scaffold, thereby expanding the prion paradigm beyond the classical model of fibril-end-mediated templating.
This study characterizes the skeletal proteome of the cold-water coral *Desmophyllum pertusum* and reveals a conserved, dynamic biomineralization toolkit shared across diverse coral taxa, redefining calcification as a coordinated cellular network resilient to environmental variation.
This study demonstrates that specific plant-derived soft electrophiles, particularly certain flavones, upregulate pro-resolving oxylipins via the NF-κB orthologue Relish in a paraquat-induced *Drosophila* model of Parkinson's disease, thereby promoting the resolution of neuroinflammation and offering potential therapeutic strategies for neurodegenerative disorders.
The RhoG G12E mutant, despite accumulating in a GTP-bound state due to impaired hydrolysis, fails to drive productive signaling and instead causes phenotypes associated with reduced RhoG activity, demonstrating that continuous nucleotide cycling rather than mere GTP occupancy is essential for RhoG function.
This study utilizes cryo-EM and phosphoproteomics to reveal that the HSP90-CDC37 chaperone system actively orchestrates RAF1 kinase activation through a unique asymmetric pre-dimerization mechanism involving stepwise folding and selective phosphorylation, thereby establishing it as a critical regulator of RAS-MAPK signaling with significant therapeutic implications.
This study establishes a comprehensive framework for optimizing liquid chromatography-mass spectrometry (LC-MS) detection of retinoids by systematically refining chromatographic, ionization, and extraction parameters, thereby enabling their reliable quantification in low-abundance biofluids like cerebrospinal fluid.
This study demonstrates that pathogenic human mitochondrial tRNA variants, particularly those near the acceptor stem, impair RNA processing by disrupting the RNase-mediated removal of 5' leader sequences, thereby providing a structural framework to predict how such mutations cause mitochondrial disease.
This study elucidates the molecular mechanisms of the ISG15-USP18-STAT2 inhibitory complex by identifying a critical STAT2-binding loop in USP18, characterizing the impact of patient mutations and viral proteins on this interaction, and thereby advancing the understanding of type I interferon signaling regulation.
This study elucidates how biomolecular condensates regulate reaction kinetics not only by concentrating reactants through excluded-volume effects but also by modulating the internal chemical microenvironment, specifically hydrophilicity and water activity, across diverse protein scaffolds.
This study utilizes time-resolved serial synchrotron crystallography (TR-SSX) combined with LAMA-based ligand delivery to visualize and quantify the diffusion-limited binding of indole to T4 lysozyme L99A, revealing how ligand occupancy evolution drives progressive F-helix rearrangement toward a dominant conformational state in real time.
This study utilizes molecular dynamics simulations to demonstrate that while partial oxidation of SARS-CoV-2 membrane lipids has a negligible effect on spike protein anchoring, extensive oxidation significantly weakens this stability by disrupting lipid order and cholesterol clusters, suggesting that lipid peroxidation acts synergistically with mechanical forces to facilitate viral inactivation.
This study establishes a quantitative framework for uridylation-mediated RNA decay in *Drosophila*, revealing how the kinetic tuning of Tailor-generated oligo(U) intermediates and the selective recognition of their specific length and accessibility by Dis3l2 collectively encode decay competence through transient RNA 3'-end states.