388 papers
This study resolves crystal structures of an ASBT homologue and a humanized version to reveal that, unlike NTCP, these SLC10 family transporters lack a transmembrane pore due to a flexible TM6 helix, and molecular dynamics simulations further demonstrate how membrane lipids facilitate the transport of bile acids with large hydrophobic groups.
This study demonstrates that magnesium acts as a master regulator of KRAS structural dynamics by stabilizing the protein fold and constraining nucleotide exchange, with distinct concentration-dependent effects on specific regions like the p-loop and switch I, thereby revealing Mg2+-sensitive hotspots as promising targets for next-generation therapeutics.
The paper introduces RIPUP, a rapid multi-protease workflow combining Arg-C Ultra and r-Chymotrypsin digestion with TMT labeling and HiP-Frag analysis to reduce histone PTM sample preparation from days to hours while significantly expanding coverage to detect previously elusive acylations and variant-specific modifications.
This study reveals that hyaluronic acid synthases are more widely distributed across the fungal kingdom than previously thought, identifying 68 putative enzymes primarily in Basidiomycota that share a common ancestor with chitin synthases but possess unique structural features, such as a three-helix transmembrane pore and an intrinsically disordered C-terminus, which may influence the regulation and function of the hyaluronic acid they produce.
This study demonstrates that stereodefined butynamide probes, despite lower intrinsic reactivity than acrylamides, uniquely target the actin-maturing protease ACTMAP in human cancer cells, thereby validating butynamides as a differentiated electrophile for expanding covalent ligand discovery.
This paper addresses the structural analysis challenges of filament-forming proteins like TasA and camelysins by proposing the engineering of N- and C-terminal truncated or extended variants to prevent self-association and enable crystallization.
This study identifies AHA, a conserved archaeal ribosome-associated factor that induces translational hibernation by bridging ribosomal subunits and structurally links bacterial ribosome silencing with eukaryotic energy sensing through its dual homology to bacterial HPF and the AMPK domain.
This study identifies AltSLC35A4, a conserved microprotein encoded by an alternative open reading frame, as a novel regulator of mitochondrial DNA homeostasis that interacts with actomyosin cytoskeletal components to maintain nucleoid spatial distribution and copy number independently of replication or bioenergetic states.
This study reveals that the bacterial persulfide dioxygenase CstB utilizes a unique self-S-sulfonation mechanism, where a dynamic loop cysteine mimics glutathione to facilitate the O2-dependent conversion of two thiol persulfides into thiosulfate, thereby enabling *Staphylococcus aureus* to detoxify reactive sulfur species while harnessing their cytoprotective benefits.
This study demonstrates that while multiple data analysis methods can correlate biochemical inhibition with antiviral activity for MERS-CoV main protease inhibitors, an enzyme kinetics model accounting for dimerization and biphasic concentration-response curves provides the most accurate prediction of cellular efficacy.
Recurrent C-terminal truncating mutations in the disordered region of the epigenetic regulator ASXL1 promote myeloid malignancies by releasing intramolecular suppression to unleash pathological biomolecular condensation, which hyperactivates BAP1-mediated H2A deubiquitination and drives leukemogenic gene expression.
This paper presents a novel sequential extraction-based multi-omics platform that enables deep, reproducible, and simultaneous characterization of proteins, lipids, and metabolites from a single small extracellular vesicle sample, overcoming material limitations and revealing purification-dependent molecular profiles to advance biomarker discovery and therapeutic applications.
This study reveals that the Rpd3L histone deacetylase complex acts as a metabolic gatekeeper in *Saccharomyces cerevisiae* by dynamically removing H3K9 acetylation from active promoters upon nutrient shifts, thereby coordinating the shutdown of growth programs and ensuring transcriptional fidelity during metabolic transitions.
This study identifies 4,5,6,7-tetrabromo-1H-benzotriazole (TBB) as a specific small-molecule inhibitor of the NADPH phosphatase MESH1 that effectively suppresses ferroptosis in vitro and reduces neuronal death in an Alzheimer's disease model, validating MESH1 as a promising therapeutic target.
This study elucidates the structural basis of arsenite efflux by presenting high-resolution cryo-EM structures of the ArsB pump from *Leptospirillum ferriphilum*, revealing an inward-facing conformation where metalloid binding occurs via hydrogen bonding and is coupled to proton transport through conserved aspartate residues.
This study identifies and structurally characterizes a unique nucleic acid-binding module called PXL within the PML-1 protein, demonstrating its selective binding to G-rich single-stranded RNA and DNA motifs and its role in modulating the transcriptome to regulate gene expression and nuclear organization.
The paper introduces OptiPrime, a mechanistic machine learning model that achieves state-of-the-art, interpretable, and generalizable prediction of prime editing outcomes across various editing strategies and cell types, thereby enabling the design of efficient therapeutic edits such as the in vivo correction of a neurological disorder in mice.
This study introduces Rapid HAMMOC, an optimized TiO2-based phosphopeptide enrichment workflow that utilizes improved loading buffers, a dual-membrane StageTip for direct desalting, and LMNG to suppress non-specific adsorption, thereby enabling highly sensitive and rapid phosphoproteomic profiling from ultra-low input samples.
This study utilizes high-resolution cryo-EM and 3D variability analysis to reveal the ATP-driven conformational dynamics and itraconazole binding mechanism of the fungal drug efflux pump Cdr1, providing a structural framework for understanding azole resistance and the chemo-mechanical cycle of ABC transporters.
This study determines the 3.4-angstrom cryo-EM structure of the FZD4-Tspan12 complex, revealing how Tspan12 facilitates FZD4 trafficking and enhances Norrin binding to amplify Wnt signaling, thereby providing a molecular basis for targeting retinal vascular diseases.