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A conserved helix-tiling architecture of urate oxidase organizes metabolism in peroxisomes

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Cells organize metabolism within a crowded intracellular milieu, yet the structural logic and functional consequences of supramolecular enzyme assemblies in vivo remain poorly defined. Here, using in situ cryo-electron tomography, we identify a previously uncharacterized high-order architecture of urate oxidase in mouse liver. Urate oxidase homotetramers assemble into helical fibers that tile laterally to form a stable, and porous lamellar scaffold. This organization preserves extensive accessible surface area while permitting efficient substrate and product exchange. Structure-guided perturbation abolishes the assembly in vivo without measurably altering intrinsic catalytic activity, indicating a primary role in spatial organization rather than allosteric regulation. Consistent with this, the assembled state enhances resistance to thermal, proteolytic and oxidative stress, supporting sustained activity in the peroxide-rich peroxisomal matrix. Conserved across mammals, this architecture reveals a strategy for metabolic compartmentalization that couples efficient catalysis to increased molecular robustness without the trade-off between supramolecular assembly and enzyme accessibility. 

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Yang, J., Chen, Z., Wang, Y., Yu, Z., Yuan, S., Sun, X., Kan, C., Du, W., Li, Z., Luo, S., Zhu, Y., Shao, X., Wang, G., Li, M., Gao, Y., Chen, X., & Guo, Q. (2026). A conserved helix-tiling architecture of urate oxidase organizes metabolism in peroxisomes. 浪淘沙预印本平台. https://doi.org/10.65215/LTSpreprints.2026.04.18.000189

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