Biochemistry & Biophysics
All Items
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Abstract:
The ALKA channel, a member of the Cys-loop ligand-gated ion channel (cysLGIC) family, has recently been identified as a receptor mediating alkaline taste sensation in Drosophila. However, the structure and molecular mechanism underlying pH sensing of ALKA channel remain to be determined. Here, we report the cryo-EM structure of ALKA, determined at a resolution of 2.86 Å under its physiological pH...
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Abstract:
Glycans are essential mediators of multiple biological processes, yet their chemical complexity and non-template-driven biosynthesis pathways pose significant challenges for the establishment of the sequence-structure relationship. Here, we report cryo-EM structures of the tubular mastigoneme from a golden alga species. A large number of N- and O-glycans are observed at 1.8-2.2 Å resolutions. We...
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Abstract:
Understanding how molecular binding couples with diffusion is fundamental to molecular engineering and biomedical applications. At the mesoscale, this coupling gives rise to a binding memory effect, characterized by power-law decays in temporal binding autocorrelations. This repeated binding-unbinding cycles transforms the static, affinity-limited binding picture into a dynamic landscape. While...
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Abstract:
The insulin receptor (IR) is central to the regulation of glucose and lipid metabolism. Although insulin is its primary ligand, insulin-like growth factors I and II (IGF-I and IGF-II) also engage IR, albeit with reduced affinity. The structural basis of cooperative ligand binding, however, has remained poorly understood. Here, we report cryo-Electron Microscopy (cryo-EM) structures of IR in...
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Abstract:
Super-resolution imaging with RhoBAST fluorogenic RNA aptamer sheds new light on decoding RNA dynamics with high spatiotemporal resolution. To uncover the molecular basis underlying its exceptional photophysical properites, we determined the first free-form structure of RhoBAST, along with its ligand-bound complexes with TMR-DN and related analogs. RhoBAST adopts an inverted 'V'-shaped...
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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,...
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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...
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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...
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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...
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Abstract:
Human M-channels, primarily assembled by heteromeric KCNQ2/KCNQ3 subunits, are critical regulators of neuronal excitability, and loss-of-function mutations in either subunit are linked to epileptic disorders. Yet, the molecular mechanisms underlying heteromeric assembly, gating, and pharmacological modulation have remained largely elusive. Here, we present high-resolution cryo-EM structures of...