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Abstract: Almost all the reported cryo-EM structures of eukaryotic voltage-gated sodium (Na v ) channels, including those of human Na v 1.1-Na v 1.8, represent various inactivated states that are characteristic of non-conductive pore domain (PD) and voltage-sensing domains (VSDs) activated to varying degrees. To capture an open-state Na v structure, we treated purified human Na v 1.7 with veratridine...
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Abstract: Single-particle cryo-electron microscopy (cryo-EM) typically requires the acquisition and analysis of a large number of micrographs to achieve high-resolution three-dimensional (3D) reconstructions of biological macromolecules. In this study, we demonstrate that when sample quality is sufficiently high, near-atomic resolution 3D density maps can be obtained using particle images from a single...
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Abstract: Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy with a complex and immunosuppressive tumor microenvironment (TME). While aggrephagy, a selective autophagy process, has been linked to cancer, its role in ccRCC remains unclear. Through integrated multi-omics analysis of single-cell and bulk sequencing data, we constructed the first aggrephagy activity atlas in ccRCC TME,...
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Abstract: The functional diversification of biosynthetic enzymes underlies the chemical richness of natural products, yet how primary metabolic enzymes evolve to acquire specialized functions in secondary metabolism remains elusive. Here, we report a tripartite enzyme complex from oral Streptococcus species—comprising 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGS), acetyl-CoA acetyltransferase...