388 papers
This study demonstrates that HIWI2 is essential for maintaining photoreceptor integrity by regulating endosomal trafficking to ensure Eph receptor stability, as its deficiency disrupts sorting pathways, accelerates receptor degradation, and impairs cell motility.
Through structure-based rational engineering of residues lining the active site, researchers successfully enhanced the glucose tolerance and kinetic properties of the fungal GH1 enzyme *Fusarium odoratissimum* -glucosidase, creating a promising candidate for industrial cellulase cocktails.
This study demonstrates that N-methylated and stapled peptide ligands can effectively stabilize the extended binding motif of LC3/GABARAP proteins, enabling the development of high-affinity, selective, and minimally charged tetrapeptide inhibitors with improved drug-like properties for targeting autophagy.
This study establishes the first continuous in vitro FRET-based kinetic assay to characterize the cholesterolysis activity of vertebrate Sonic Hedgehog C-terminal domains, revealing their strict substrate stereospecificity, optimal zwitterionic detergent conditions, and the ability to chemically rescue a catalytic mutant with hyper-nucleophilic sterols.
This study demonstrates that replacing alcohol oxidase with alcohol dehydrogenase (Adh2) for methanol dissimilation in *Komagataella phaffii* significantly enhances carbon efficiency, biomass yield, and product titers in synthetic autotrophic strains by coupling methanol oxidation with NADH generation.
This study reveals that PD1 engagement triggers Shp2 to undergo liquid-liquid phase separation, forming dynamic condensates that selectively partition inhibitory substrates like CD3{zeta} and CD28 to organize signalosomes and suppress T cell activation.
This study elucidates the mechanism by which the Varicella Zoster Virus protein ORF61 functions as a SUMO-targeted ubiquitin ligase, revealing that it utilizes a high-affinity C-terminal SIM to bind SUMO chains and co-opts the E2D family to synthesize branched polyubiquitin chains (K11, K48, and K63) for dispersing PML nuclear bodies and repressing viral gene expression.
This study elucidates the structural and evolutionary mechanisms of DAF-12 coactivator recruitment in parasitic nematodes through multi-disciplinary approaches, revealing both conserved features shared with mammalian receptors and parasite-specific interactions that offer a new framework for developing antiparasitic therapies targeting this critical developmental switch.
This study reveals that four interdependent pseudoknots at the 3'-terminus of the West Nile virus genome function synergistically to regulate viral growth and sfRNA formation, with SLIV playing the dominant role, and identifies conserved tertiary motifs within this assembly as potential targets for pan-flaviviral therapeutics.
This study utilizes a multi-level proteomic analysis to investigate the molecular basis of iodine-based micro-CT contrast, finding that while specific structural proteins are rich in iodine-binding aromatic heterocyclic amino acids, no significant correlation exists between overall heterocycle enrichment and tissue-specific staining intensity.
This study combines comparative genomics and pilot functional experiments to propose that certain "suicide" thiazole synthases (Thi4) may operate in a non-suicide mode by utilizing external persulfide or thiocarboxylate sulfur donors rather than sacrificing their own active-site cysteine, challenging the traditional view of their irreversible inactivation mechanism.
By integrating global marine metagenomic datasets with machine learning, this study maps the biogeography and taxonomic drivers of key nitrogen metabolism pathways, revealing distinct environmental patterns that link specific microbial groups to aerobic and anaerobic processes to improve biogeochemical models.
This study elucidates the molecular determinants of ligand selectivity and sensitivity in the *Daphnia magna* dopamine-gated cation channel (Dm-DopC1) by identifying specific mutations in binding loops that govern catecholamine responsiveness and reveal the receptor's hybrid pharmacological profile, thereby providing insights into the evolutionary flexibility of pentameric ligand-gated ion channels.
The study characterizes 4-methyl-3-aminopyridine (4Me3AP) as a novel, potent, and less toxic voltage-gated potassium channel blocker with improved pharmacokinetic properties compared to 4-aminopyridine, suggesting its potential for treating demyelinating diseases.
This study introduces a novel Nτ-propargylated histamine probe to overcome the limitations of existing antibodies, enabling the first chemical proteomic profiling of the histaminylation proteome in cancer cells and the discovery of previously uncharacterized TGM2-catalyzed epigenetic marks on core histones.
This study identifies LJY-3-60 as a novel molecular glue that induces CRBN homodimerization via a non-canonical interface, triggering intrinsic CRL4CRBN-mediated autodegradation and offering a controllable strategy to mitigate PROTAC toxicity.
By integrating deep proteomic and ubiquitinomic profiling of a 960-compound library with interpretable machine learning, this study systematically expands the CRBN neosubstrate landscape to include over 124 new targets and establishes design principles for the rational development of next-generation molecular glue degraders.
This study demonstrates that serum from critically ill COVID-19 patients induces specific proteomic changes in olfactory neuroepithelial stem cells that mimic molecular pathways associated with post-COVID neurological complications, thereby offering new insights into the mechanisms underlying Long COVID.
By dimerizing the natural product Rocaglamide into a new ligand called BisRoc, researchers created a more potent and selective inhibitor that bridges eIF4A proteins to RNA, forming higher-order complexes that effectively suppress translation and promote stress-granule formation.
This study utilizes a novel sortase-mediated chemical-ligation strategy to generate sulfated Duffy antigen receptor (DARC) and determine its high-resolution cryo-EM structures with chemokines CCL7 and CXCL8, revealing a unique single-site binding mechanism distinct from other chemokine receptors and elucidating how tyrosine sulfation and Fya/Fyb allelic variations modulate binding affinity through specific N-terminus repositioning.