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Updated: Apr 8, 2026

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
Reprogramming Cascade Catalysis via Protein-Directed Interfacial Assembly of Spatially Ordered Clusterzymes for
Fengjie Hao1, Juntao Hu1, Ziyu Kuai1
1Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Abstract:
Precise spatial arrangement of catalytic centers is essential to emulate the efficiency of natural enzymatic cascades. Herein, we report a protein-mediated interfacial self-assembly strategy to construct vesicle-like proteinosomes with spatially arranged gold clusterzymes (AuNEs) to enhance multienzyme cascade catalysis. AuNEs were synthesized in situ within the confined cavity of a stable cyclic SP1 protein scaffold, genetically engineered with a Cysteine-Cysteine-Tyrosine (CCY) peptide to control cluster nucleation and growth. Metal doping with copper (Cu) and cadmium (Cd) yielded catalytically distinct Au-CuNEs and Au-CdNEs, exhibiting superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)-like activities. These functionally complementary clusterzymes coassembled into size-tunable, ordered proteinosomes via electrostatic interactions with cetyltrimethylammonium bromide, enabling dense catalytic packing and proximity-enhanced reactions. The resulting proteinosomes displayed efficient cellular uptake and significantly improved reactive oxygen species (ROS) scavenging in Caenorhabditis elegans. This work presents a spatially programmable platform for synergistic catalysis, offering a promising approach for treating ROS-related diseases.
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