375 papers
This study employs multi-temperature X-ray crystallography to reveal previously hidden, temperature-dependent conformational states of K-RAS, including critical allosteric and druggable sites that are obscured under standard cryogenic conditions, thereby offering a new framework for rational drug design against this challenging oncogenic target.
By combining AI-based structural models with molecular dynamics simulations, this study reveals that human rhomboid proteases exhibit diverse lateral gating mechanisms, where orphan family members possess unusually narrow gates requiring high energy to open, thereby explaining their lack of identified substrates.
By applying high-throughput microfluidic enzyme kinetics to profile 190 SHP2 variants, this study reveals that dysregulated autoinhibition—not altered stability or catalysis—is the primary driver of pathogenesis and explains how allosteric inhibitors differentially stabilize specific conformations to modulate drug responses.
By combining systematic in vivo isotope tracing with a biosynthesis-aware AI model, this study maps the origins of thousands of unidentified mammalian metabolites, revealing novel metabolic families and linking the age-related depletion of specific isoprenoids to impaired coenzyme A synthesis.
This paper introduces a quantitative workflow combining live-cell measurements with advanced in vitro spectroscopy to reveal that fluorescent protein photobleaching involves complex, heterogeneous chemical transformations beyond simple ON-OFF switching, thereby providing new insights and indicators to mitigate biases in quantitative imaging techniques like FLIM and FRET.
This study elucidates the structure-interaction relationship between polymyxin lipopeptides and the human oligopeptide transporter hPepT2 through integrated computational and experimental approaches, identifying critical binding residues and demonstrating that specific analogues with reduced hPepT2 interaction retain antibacterial efficacy while significantly lowering nephrotoxicity.
This study demonstrates that the conserved, highly structured SL1-4b region of the SARS-CoV-2 5'-UTR potently activates the innate immune sensor OAS1, with SL4 serving as the primary interaction site and surrounding structural elements facilitating optimal activation.
This study identifies the phosphatase PPM1D as a critical regulator that facilitates the restart of stalled DNA replication forks by restraining excessive ATM signaling, thereby preventing detrimental nucleolytic degradation and ensuring proper RAD51 recruitment.
This study demonstrates that the dynamic assembly and dissociation of the yeast mitochondrial MDH1-CIT1 metabolon are regulated by respiratory activity, mitochondrial matrix pH, and specific metabolite levels, serving as a key mechanism for TCA cycle adaptation to cellular metabolic demands.
This study reveals that structurally distinct nanobodies targeting the *Pseudomonas aeruginosa* virulence factor Cif employ convergent recognition strategies involving a 90-degree domain rotation and aromatic residue insertion to sterically block the enzyme's active site, demonstrating the immune system's ability to solve constrained molecular recognition challenges through fundamentally different solutions.
Cold acclimation prevents hepatic steatosis despite increased lipid influx from adipose tissue by reprogramming hepatic lipid composition toward n-3 highly unsaturated fatty acids, which suppresses monounsaturated fatty acid synthesis and triglyceride assembly, thereby reshaping systemic lipid distribution.
This study presents a machine learning-assisted ATR-FTIR spectroscopy approach that enables rapid, label-free, and reagent-free quantification of tumour biomarkers, particularly CA125, in human serum with high accuracy, offering a promising alternative to traditional immunoassays for resource-limited clinical settings.
This study reveals that the eukaryotic chaperonin TRiC folds the oversized ciliary protein IFT172 through a non-canonical "fold-and-eject" mechanism involving chamber expansion and concurrent HSP70 assistance, challenging the classical view of the closed chamber as an obligate folding cage and establishing a new paradigm for ciliary biogenesis.
This study reveals that Acyl Carrier Protein (ACP) is essential for blood-stage *Plasmodium falciparum* survival not through its canonical role in fatty acid synthesis, but by stabilizing pyruvate kinase II (PKII), a critical enzyme required for apicoplast biogenesis and isoprenoid precursor biosynthesis.
This study combines Force Profile Analysis and molecular dynamics simulations to demonstrate how specific single residues within a nascent polypeptide chain interact with the ribosome exit tunnel to modulate translational arrest forces, revealing that large hydrophobic residues generally promote stalling release while specific residues like asparagine can stabilize the stalled state through interactions with ribosomal protein uL22.
This study demonstrates that tubulin glycylation acts as a critical regulator of ciliary stability and intraflagellar transport by selectively enhancing kinesin-2 motility, suppressing kinesin-1 activity, and protecting microtubules from depolymerization and severing through distinct combinatorial modification patterns.
This study demonstrates that the native Finnish wild hop genotype LUKE 2541 exhibits solvent- and tissue-specific bioactivities, with water extracts effectively inhibiting Gram-positive bacteria and non-polar cone extracts showing potent, dose-dependent antiproliferative effects against human cancer cell lines, particularly colorectal cells.
This study elucidates the molecular mechanism of SARS-CoV-2 neurotropism by resolving the cryo-EM structure and quantifying the nanomolar affinity interaction between the viral spike protein and the neuronal co-receptor contactin 1, revealing how the virus binds to the nervous system via a unique interface that overlaps with neutralizing antibody epitopes.
This study reveals that the DEAD-box helicase Vasa is activated in a spatially restricted manner by eLOTUS-domain proteins, which bind to Vasa's open conformation and utilize a positively charged disordered region to accelerate RNA engagement, thereby gating enzymatic activity to specific cytoplasmic granules essential for germline function.
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.