All Items
-
Abstract:
The transport of molecules across biological membranes is essential for life, allowing cells to acquire nutrients, remove waste, maintain cellular homeostasis and communicate with their environment. Although there have been advances in de novo design of functional transmembrane proteins, designing synthetic transporters that robustly and selectively transport specific small molecules across...
-
Abstract: Resolving compositional and conformational heterogeneity remains a fundamental bottleneck in single-particle cryo-EM. This challenge stems from a circular dependency: classification requires reliable references, while reference generation requires accurate classification. Current deep learning methods often resort to blind stochastic initialization, frequently becoming trapped in local minima...
-
Abstract:
Exosomes, as key mediators of intercellular communication, have demonstrated great potential in drug delivery. However, their accurate characterization remains challenging due to their complex physical properties. This study purified exosomes from milk and human urine using ultracentrifugation and the EXODUS systems and systematically compared several biophysical techniques to characterize them,...
-
Abstract:
Fatty acids (FAs) are essential biomolecules that play critical roles in development and growth. Fatty acid transport proteins (FATPs) are responsible for the transport of long-chain FAs (LCFAs) and very-long-chain FAs (VLCFAs), exhibiting bifunctionality that includes both FA transport and acyl-CoA synthetase activity. FATPs are potential drug targets for treating various metabolism-related...
-
Abstract:
Cells must eliminate various unwanted organelles to maintain homeostasis, yet how they achieve this when their primary degradation system, the lysosome, is impaired remains poorly understood. Here, we discover cytopurgosis, a lysosome-independent organelle-removal pathway that expels multiple organelles, including entire lysosomes, within large extracellular vesicles that we termed "purgasomes"....
-
Abstract:
Historical records of wildlife are important information in understanding their historical distribution patterns and indigenous knowledge of wildlife in traditional cultures, and have significant academic value and practical implications for the conservation of wildlife. However, the complex system of animal names and numerous synonyms in historical documents often complicates the identification...
-
Abstract:
The human Ether-a-go-go Related Gene (hERG)-encoded potassium channel is critical for cardiac ventricular action potential repolarization and serves as a core target for preclinical drug safety screening. The lack of stable, high-expression hERG cell models has limited the reliability and throughput of functional assays for hERG channel evaluation. Thus, developing a robust stable hERG-expressing...
-
Abstract:
Antibody-dependent enhancement (ADE) of viral entry remains a mechanistically unresolved phenomenon in SARS-CoV-2 variants, with its variant-specificity and pathological consequences poorly defined. Through systematic profiling of 114 monoclonal antibodies (mAbs) across major variants of concern (VOCs), we discover that the Delta variant exhibits uniquely potent ADE mediated by mAbs targeting...
-
Abstract:
The heteromeric KCNQ2/3 channel constitutes the molecular correlate of the neuronal M-current, a potassium conductance essential for stabilizing resting membrane potential and controlling neuronal excitability. Despite its physiological and therapeutic importance, the structural basis for its unique functional properties—distinct from homomeric KCNQ2 or KCNQ3—has remained enigmatic, and its...
-
Abstract: Conserved TIR domain proteins play essential roles in immune signaling, development, and neurodegeneration. Here, we identify Raw as a member of a distinct TIR protein family that functions as a cADPR-specific hydrolase, with catalytic mutations phenocopying delayed axon degeneration. While Raw and dSarm synergistically deplete NAD to drive axon degeneration, they antagonistically regulate cADPR...