A conserved urate oxidase helix-tiling assembly promotes metabolic robustness in peroxisomes
Nov. 11, 2026
Dr. Qiang Guo published a paper in Nature Chemical Biology with his collaborators.
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, 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.
Original Link: https://www.nature.com/articles/s41589-026-02372-1